Atezolizumab potentiates Tcell-mediated cytotoxicity and coordinates with FAK to suppress cell invasion and motility in PD-L1+ triple negative breast cancer cells
Identifieur interne : 000941 ( Ncbi/Merge ); précédent : 000940; suivant : 000942Atezolizumab potentiates Tcell-mediated cytotoxicity and coordinates with FAK to suppress cell invasion and motility in PD-L1+ triple negative breast cancer cells
Auteurs : Nishant Mohan [États-Unis] ; Salman Hosain [États-Unis] ; Jun Zhao [États-Unis] ; Yi Shen [États-Unis] ; Xiao Luo [États-Unis] ; Jiangsong Jiang [États-Unis] ; Yukinori Endo [États-Unis] ; Wen Jin Wu [États-Unis]Source :
- Oncoimmunology [ 2162-4011 ] ; 2019.
Abstract
Immune check point inhibitors targeting programmed cell death protein-1 (PD-1) and its ligand (PD-L1) have shown clinical success in treatment of human malignancies. Triple negative breast cancer (TNBC), which is primarily characterized by high heterogeneity and presence of tumor infiltrating lymphocytes, remains therapeutic challenge due to unavailability of approved targeted therapy. Therapeutic potential of immune check point inhibitors for TNBC patients is under active clinical investigation. In this study, we show that FDA-approved anti-PD-L1 antibody, atezolizumab (ATE), potentiates T cell-mediated cytotoxicity and apoptosis of TNBC cells that express higher levels of PD-L1, but does not have significant effect on TNBC cells expressing low levels of PD-L1. PD-L1 knockdown further confirmed that ability of ATE to promote T cell-induced cytotoxicity is PD-L1 expression dependent. Combination of ATE with PD-L1 upregulating agents, such as HDAC, proteasomal, and lysosomal inhibitors, further augmented cytotoxic activity of T cells toward TNBC cells. Based on analysis of breast cancer tissue samples deposited in The Cancer Genome Atlas (TCGA), we found a positive correlation between PD-L1 and focal adhesion kinase (FAK) mRNA expression in PD-L1-positive (PD-L1+) TNBC, suggesting a functional association of FAK and immune checkpoints. We further demonstrate that ATE dramatically downregulates phosphorylation status of FAK, an important regulator of cell invasion and migration, and significantly enhances FAK inhibitor mediated inhibition of cell motility and invasion of PD-L1+ TNBC cells independent of T cells. Taken together, our data suggest that ATE shows promising anti-tumor activity in PD-L1+ TNBC via both T cell-dependent and -independent mechanisms.
Url:
DOI: 10.1080/2162402X.2019.1624128
PubMed: 31428520
PubMed Central: 6685513
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: 000749
- to stream Pmc, to step Curation: 000749
- to stream Pmc, to step Checkpoint: 000986
Links to Exploration step
PMC:6685513Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Atezolizumab potentiates Tcell-mediated cytotoxicity and coordinates with FAK to suppress cell invasion and motility in PD-L1<sup>+</sup>
triple negative breast cancer cells</title>
<author><name sortKey="Mohan, Nishant" sort="Mohan, Nishant" uniqKey="Mohan N" first="Nishant" last="Mohan">Nishant Mohan</name>
<affiliation wicri:level="1"><nlm:aff id="AFF0001"><institution>Division of Biotechnology Review and Research I, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration</institution>
, Silver Spring, Maryland,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Hosain, Salman" sort="Hosain, Salman" uniqKey="Hosain S" first="Salman" last="Hosain">Salman Hosain</name>
<affiliation wicri:level="1"><nlm:aff id="AFF0001"><institution>Division of Biotechnology Review and Research I, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration</institution>
, Silver Spring, Maryland,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Zhao, Jun" sort="Zhao, Jun" uniqKey="Zhao J" first="Jun" last="Zhao">Jun Zhao</name>
<affiliation wicri:level="1"><nlm:aff id="AFF0001"><institution>Division of Biotechnology Review and Research I, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration</institution>
, Silver Spring, Maryland,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="AFF0002"><institution>Interagency Oncology Task Force (IOTF) Fellowship: Oncology Product Research/Review Fellow, National Cancer Institute</institution>
, Bethesda, Maryland,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Shen, Yi" sort="Shen, Yi" uniqKey="Shen Y" first="Yi" last="Shen">Yi Shen</name>
<affiliation wicri:level="1"><nlm:aff id="AFF0001"><institution>Division of Biotechnology Review and Research I, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration</institution>
, Silver Spring, Maryland,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Luo, Xiao" sort="Luo, Xiao" uniqKey="Luo X" first="Xiao" last="Luo">Xiao Luo</name>
<affiliation wicri:level="1"><nlm:aff id="AFF0001"><institution>Division of Biotechnology Review and Research I, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration</institution>
, Silver Spring, Maryland,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Jiang, Jiangsong" sort="Jiang, Jiangsong" uniqKey="Jiang J" first="Jiangsong" last="Jiang">Jiangsong Jiang</name>
<affiliation wicri:level="1"><nlm:aff id="AFF0001"><institution>Division of Biotechnology Review and Research I, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration</institution>
, Silver Spring, Maryland,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Endo, Yukinori" sort="Endo, Yukinori" uniqKey="Endo Y" first="Yukinori" last="Endo">Yukinori Endo</name>
<affiliation wicri:level="1"><nlm:aff id="AFF0001"><institution>Division of Biotechnology Review and Research I, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration</institution>
, Silver Spring, Maryland,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Wu, Wen Jin" sort="Wu, Wen Jin" uniqKey="Wu W" first="Wen Jin" last="Wu">Wen Jin Wu</name>
<affiliation wicri:level="1"><nlm:aff id="AFF0001"><institution>Division of Biotechnology Review and Research I, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration</institution>
, Silver Spring, Maryland,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">31428520</idno>
<idno type="pmc">6685513</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6685513</idno>
<idno type="RBID">PMC:6685513</idno>
<idno type="doi">10.1080/2162402X.2019.1624128</idno>
<date when="2019">2019</date>
<idno type="wicri:Area/Pmc/Corpus">000749</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000749</idno>
<idno type="wicri:Area/Pmc/Curation">000749</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000749</idno>
<idno type="wicri:Area/Pmc/Checkpoint">000986</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000986</idno>
<idno type="wicri:Area/Ncbi/Merge">000941</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Atezolizumab potentiates Tcell-mediated cytotoxicity and coordinates with FAK to suppress cell invasion and motility in PD-L1<sup>+</sup>
triple negative breast cancer cells</title>
<author><name sortKey="Mohan, Nishant" sort="Mohan, Nishant" uniqKey="Mohan N" first="Nishant" last="Mohan">Nishant Mohan</name>
<affiliation wicri:level="1"><nlm:aff id="AFF0001"><institution>Division of Biotechnology Review and Research I, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration</institution>
, Silver Spring, Maryland,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Hosain, Salman" sort="Hosain, Salman" uniqKey="Hosain S" first="Salman" last="Hosain">Salman Hosain</name>
<affiliation wicri:level="1"><nlm:aff id="AFF0001"><institution>Division of Biotechnology Review and Research I, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration</institution>
, Silver Spring, Maryland,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Zhao, Jun" sort="Zhao, Jun" uniqKey="Zhao J" first="Jun" last="Zhao">Jun Zhao</name>
<affiliation wicri:level="1"><nlm:aff id="AFF0001"><institution>Division of Biotechnology Review and Research I, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration</institution>
, Silver Spring, Maryland,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="AFF0002"><institution>Interagency Oncology Task Force (IOTF) Fellowship: Oncology Product Research/Review Fellow, National Cancer Institute</institution>
, Bethesda, Maryland,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Shen, Yi" sort="Shen, Yi" uniqKey="Shen Y" first="Yi" last="Shen">Yi Shen</name>
<affiliation wicri:level="1"><nlm:aff id="AFF0001"><institution>Division of Biotechnology Review and Research I, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration</institution>
, Silver Spring, Maryland,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Luo, Xiao" sort="Luo, Xiao" uniqKey="Luo X" first="Xiao" last="Luo">Xiao Luo</name>
<affiliation wicri:level="1"><nlm:aff id="AFF0001"><institution>Division of Biotechnology Review and Research I, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration</institution>
, Silver Spring, Maryland,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Jiang, Jiangsong" sort="Jiang, Jiangsong" uniqKey="Jiang J" first="Jiangsong" last="Jiang">Jiangsong Jiang</name>
<affiliation wicri:level="1"><nlm:aff id="AFF0001"><institution>Division of Biotechnology Review and Research I, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration</institution>
, Silver Spring, Maryland,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Endo, Yukinori" sort="Endo, Yukinori" uniqKey="Endo Y" first="Yukinori" last="Endo">Yukinori Endo</name>
<affiliation wicri:level="1"><nlm:aff id="AFF0001"><institution>Division of Biotechnology Review and Research I, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration</institution>
, Silver Spring, Maryland,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Wu, Wen Jin" sort="Wu, Wen Jin" uniqKey="Wu W" first="Wen Jin" last="Wu">Wen Jin Wu</name>
<affiliation wicri:level="1"><nlm:aff id="AFF0001"><institution>Division of Biotechnology Review and Research I, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration</institution>
, Silver Spring, Maryland,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
</analytic>
<series><title level="j">Oncoimmunology</title>
<idno type="ISSN">2162-4011</idno>
<idno type="eISSN">2162-402X</idno>
<imprint><date when="2019">2019</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><title>ABSTRACT</title>
<p>Immune check point inhibitors targeting programmed cell death protein-1 (PD-1) and its ligand (PD-L1) have shown clinical success in treatment of human malignancies. Triple negative breast cancer (TNBC), which is primarily characterized by high heterogeneity and presence of tumor infiltrating lymphocytes, remains therapeutic challenge due to unavailability of approved targeted therapy. Therapeutic potential of immune check point inhibitors for TNBC patients is under active clinical investigation. In this study, we show that FDA-approved anti-PD-L1 antibody, atezolizumab (ATE), potentiates T cell-mediated cytotoxicity and apoptosis of TNBC cells that express higher levels of PD-L1, but does not have significant effect on TNBC cells expressing low levels of PD-L1. PD-L1 knockdown further confirmed that ability of ATE to promote T cell-induced cytotoxicity is PD-L1 expression dependent. Combination of ATE with PD-L1 upregulating agents, such as HDAC, proteasomal, and lysosomal inhibitors, further augmented cytotoxic activity of T cells toward TNBC cells. Based on analysis of breast cancer tissue samples deposited in The Cancer Genome Atlas (TCGA), we found a positive correlation between PD-L1 and focal adhesion kinase (FAK) mRNA expression in PD-L1-positive (PD-L1<sup>+</sup>
) TNBC, suggesting a functional association of FAK and immune checkpoints. We further demonstrate that ATE dramatically downregulates phosphorylation status of FAK, an important regulator of cell invasion and migration, and significantly enhances FAK inhibitor mediated inhibition of cell motility and invasion of PD-L1<sup>+</sup>
TNBC cells independent of T cells. Taken together, our data suggest that ATE shows promising anti-tumor activity in PD-L1<sup>+</sup>
TNBC via both T cell-dependent and -independent mechanisms.</p>
</div>
</front>
<back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Lehmann, Bd" uniqKey="Lehmann B">BD Lehmann</name>
</author>
<author><name sortKey="Bauer, Ja" uniqKey="Bauer J">JA Bauer</name>
</author>
<author><name sortKey="Chen, X" uniqKey="Chen X">X Chen</name>
</author>
<author><name sortKey="Sanders, Me" uniqKey="Sanders M">ME Sanders</name>
</author>
<author><name sortKey="Chakravarthy, Ab" uniqKey="Chakravarthy A">AB Chakravarthy</name>
</author>
<author><name sortKey="Shyr, Y" uniqKey="Shyr Y">Y Shyr</name>
</author>
<author><name sortKey="Pietenpol, Ja" uniqKey="Pietenpol J">JA. Pietenpol</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Bianchini, G" uniqKey="Bianchini G">G Bianchini</name>
</author>
<author><name sortKey="Balko, Jm" uniqKey="Balko J">JM Balko</name>
</author>
<author><name sortKey="Mayer, Ia" uniqKey="Mayer I">IA Mayer</name>
</author>
<author><name sortKey="Sanders, Me" uniqKey="Sanders M">ME Sanders</name>
</author>
<author><name sortKey="Gianni, L" uniqKey="Gianni L">L Gianni</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Foulkes, Wd" uniqKey="Foulkes W">WD Foulkes</name>
</author>
<author><name sortKey="Smith, Ie" uniqKey="Smith I">IE Smith</name>
</author>
<author><name sortKey="Reis Filho, Js" uniqKey="Reis Filho J">JS Reis-Filho</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Adams, S" uniqKey="Adams S">S Adams</name>
</author>
<author><name sortKey="Gray, Rj" uniqKey="Gray R">RJ Gray</name>
</author>
<author><name sortKey="Demaria, S" uniqKey="Demaria S">S Demaria</name>
</author>
<author><name sortKey="Goldstein, L" uniqKey="Goldstein L">L Goldstein</name>
</author>
<author><name sortKey="Perez, Ea" uniqKey="Perez E">EA Perez</name>
</author>
<author><name sortKey="Shulman, Ln" uniqKey="Shulman L">LN Shulman</name>
</author>
<author><name sortKey="Martino, S" uniqKey="Martino S">S Martino</name>
</author>
<author><name sortKey="Wang, M" uniqKey="Wang M">M Wang</name>
</author>
<author><name sortKey="Jones, Ve" uniqKey="Jones V">VE Jones</name>
</author>
<author><name sortKey="Saphner, Tj" uniqKey="Saphner T">TJ Saphner</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Liu, S" uniqKey="Liu S">S Liu</name>
</author>
<author><name sortKey="Lachapelle, J" uniqKey="Lachapelle J">J Lachapelle</name>
</author>
<author><name sortKey="Leung, S" uniqKey="Leung S">S Leung</name>
</author>
<author><name sortKey="Gao, D" uniqKey="Gao D">D Gao</name>
</author>
<author><name sortKey="Foulkes, Wd" uniqKey="Foulkes W">WD Foulkes</name>
</author>
<author><name sortKey="Nielsen, To" uniqKey="Nielsen T">TO Nielsen</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Kato, T" uniqKey="Kato T">T Kato</name>
</author>
<author><name sortKey="Park, J" uniqKey="Park J">J Park</name>
</author>
<author><name sortKey="Kiyotani, K" uniqKey="Kiyotani K">K Kiyotani</name>
</author>
<author><name sortKey="Ikeda, Y" uniqKey="Ikeda Y">Y Ikeda</name>
</author>
<author><name sortKey="Miyoshi, Y" uniqKey="Miyoshi Y">Y Miyoshi</name>
</author>
<author><name sortKey="Nakamura, Y" uniqKey="Nakamura Y">Y Nakamura</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Pardoll, Dm" uniqKey="Pardoll D">DM Pardoll</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Dong, H" uniqKey="Dong H">H Dong</name>
</author>
<author><name sortKey="Strome, Se" uniqKey="Strome S">SE Strome</name>
</author>
<author><name sortKey="Salomao, Dr" uniqKey="Salomao D">DR Salomao</name>
</author>
<author><name sortKey="Tamura, H" uniqKey="Tamura H">H Tamura</name>
</author>
<author><name sortKey="Hirano, F" uniqKey="Hirano F">F Hirano</name>
</author>
<author><name sortKey="Flies, Db" uniqKey="Flies D">DB Flies</name>
</author>
<author><name sortKey="Roche, Pc" uniqKey="Roche P">PC Roche</name>
</author>
<author><name sortKey="Lu, J" uniqKey="Lu J">J Lu</name>
</author>
<author><name sortKey="Zhu, G" uniqKey="Zhu G">G Zhu</name>
</author>
<author><name sortKey="Tamada, K" uniqKey="Tamada K">K Tamada</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Hirano, F" uniqKey="Hirano F">F Hirano</name>
</author>
<author><name sortKey="Kaneko, K" uniqKey="Kaneko K">K Kaneko</name>
</author>
<author><name sortKey="Tamura, H" uniqKey="Tamura H">H Tamura</name>
</author>
<author><name sortKey="Dong, H" uniqKey="Dong H">H Dong</name>
</author>
<author><name sortKey="Wang, S" uniqKey="Wang S">S Wang</name>
</author>
<author><name sortKey="Ichikawa, M" uniqKey="Ichikawa M">M Ichikawa</name>
</author>
<author><name sortKey="Rietz, C" uniqKey="Rietz C">C Rietz</name>
</author>
<author><name sortKey="Flies, Db" uniqKey="Flies D">DB Flies</name>
</author>
<author><name sortKey="Lau, Js" uniqKey="Lau J">JS Lau</name>
</author>
<author><name sortKey="Zhu, G" uniqKey="Zhu G">G Zhu</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Iwai, Y" uniqKey="Iwai Y">Y Iwai</name>
</author>
<author><name sortKey="Ishida, M" uniqKey="Ishida M">M Ishida</name>
</author>
<author><name sortKey="Tanaka, Y" uniqKey="Tanaka Y">Y Tanaka</name>
</author>
<author><name sortKey="Okazaki, T" uniqKey="Okazaki T">T Okazaki</name>
</author>
<author><name sortKey="Honjo, T" uniqKey="Honjo T">T Honjo</name>
</author>
<author><name sortKey="Minato, N" uniqKey="Minato N">N Minato</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Abril Rodriguez, G" uniqKey="Abril Rodriguez G">G Abril-Rodriguez</name>
</author>
<author><name sortKey="Ribas, A" uniqKey="Ribas A">A Ribas</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Sharma, P" uniqKey="Sharma P">P Sharma</name>
</author>
<author><name sortKey="Hu Lieskovan, S" uniqKey="Hu Lieskovan S">S Hu-Lieskovan</name>
</author>
<author><name sortKey="Wargo, Ja" uniqKey="Wargo J">JA Wargo</name>
</author>
<author><name sortKey="Ribas, A" uniqKey="Ribas A">A Ribas</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Lau, J" uniqKey="Lau J">J Lau</name>
</author>
<author><name sortKey="Cheung, J" uniqKey="Cheung J">J Cheung</name>
</author>
<author><name sortKey="Navarro, A" uniqKey="Navarro A">A Navarro</name>
</author>
<author><name sortKey="Lianoglou, S" uniqKey="Lianoglou S">S Lianoglou</name>
</author>
<author><name sortKey="Haley, B" uniqKey="Haley B">B Haley</name>
</author>
<author><name sortKey="Totpal, K" uniqKey="Totpal K">K Totpal</name>
</author>
<author><name sortKey="Sanders, L" uniqKey="Sanders L">L Sanders</name>
</author>
<author><name sortKey="Koeppen, H" uniqKey="Koeppen H">H Koeppen</name>
</author>
<author><name sortKey="Caplazi, P" uniqKey="Caplazi P">P Caplazi</name>
</author>
<author><name sortKey="Mcbride, J" uniqKey="Mcbride J">J McBride</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Mittendorf, Ea" uniqKey="Mittendorf E">EA Mittendorf</name>
</author>
<author><name sortKey="Philips, Av" uniqKey="Philips A">AV Philips</name>
</author>
<author><name sortKey="Meric Bernstam, F" uniqKey="Meric Bernstam F">F Meric-Bernstam</name>
</author>
<author><name sortKey="Qiao, N" uniqKey="Qiao N">N Qiao</name>
</author>
<author><name sortKey="Wu, Y" uniqKey="Wu Y">Y Wu</name>
</author>
<author><name sortKey="Harrington, S" uniqKey="Harrington S">S Harrington</name>
</author>
<author><name sortKey="Su, X" uniqKey="Su X">X Su</name>
</author>
<author><name sortKey="Wang, Y" uniqKey="Wang Y">Y Wang</name>
</author>
<author><name sortKey="Gonzalez Angulo, Am" uniqKey="Gonzalez Angulo A">AM Gonzalez-Angulo</name>
</author>
<author><name sortKey="Akcakanat, A" uniqKey="Akcakanat A">A Akcakanat</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Wimberly, H" uniqKey="Wimberly H">H Wimberly</name>
</author>
<author><name sortKey="Brown, Jr" uniqKey="Brown J">JR Brown</name>
</author>
<author><name sortKey="Schalper, K" uniqKey="Schalper K">K Schalper</name>
</author>
<author><name sortKey="Haack, H" uniqKey="Haack H">H Haack</name>
</author>
<author><name sortKey="Silver, Mr" uniqKey="Silver M">MR Silver</name>
</author>
<author><name sortKey="Nixon, C" uniqKey="Nixon C">C Nixon</name>
</author>
<author><name sortKey="Bossuyt, V" uniqKey="Bossuyt V">V Bossuyt</name>
</author>
<author><name sortKey="Pusztai, L" uniqKey="Pusztai L">L Pusztai</name>
</author>
<author><name sortKey="Lannin, Dr" uniqKey="Lannin D">DR Lannin</name>
</author>
<author><name sortKey="Rimm, Dl" uniqKey="Rimm D">DL Rimm</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Rosenberg, Je" uniqKey="Rosenberg J">JE Rosenberg</name>
</author>
<author><name sortKey="Hoffman Censits, J" uniqKey="Hoffman Censits J">J Hoffman-Censits</name>
</author>
<author><name sortKey="Powles, T" uniqKey="Powles T">T Powles</name>
</author>
<author><name sortKey="Van Der Heijden, Ms" uniqKey="Van Der Heijden M">MS van der Heijden</name>
</author>
<author><name sortKey="Balar, Av" uniqKey="Balar A">AV Balar</name>
</author>
<author><name sortKey="Necchi, A" uniqKey="Necchi A">A Necchi</name>
</author>
<author><name sortKey="Dawson, N" uniqKey="Dawson N">N Dawson</name>
</author>
<author><name sortKey="O Onnell, Ph" uniqKey="O Onnell P">PH O’Donnell</name>
</author>
<author><name sortKey="Balmanoukian, A" uniqKey="Balmanoukian A">A Balmanoukian</name>
</author>
<author><name sortKey="Loriot, Y" uniqKey="Loriot Y">Y Loriot</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Rittmeyer, A" uniqKey="Rittmeyer A">A Rittmeyer</name>
</author>
<author><name sortKey="Barlesi, F" uniqKey="Barlesi F">F Barlesi</name>
</author>
<author><name sortKey="Waterkamp, D" uniqKey="Waterkamp D">D Waterkamp</name>
</author>
<author><name sortKey="Park, K" uniqKey="Park K">K Park</name>
</author>
<author><name sortKey="Ciardiello, F" uniqKey="Ciardiello F">F Ciardiello</name>
</author>
<author><name sortKey="Von Pawel, J" uniqKey="Von Pawel J">J von Pawel</name>
</author>
<author><name sortKey="Gadgeel, Sm" uniqKey="Gadgeel S">SM Gadgeel</name>
</author>
<author><name sortKey="Hida, T" uniqKey="Hida T">T Hida</name>
</author>
<author><name sortKey="Kowalski, Dm" uniqKey="Kowalski D">DM Kowalski</name>
</author>
<author><name sortKey="Dols, Mc" uniqKey="Dols M">MC Dols</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Herbst, Rs" uniqKey="Herbst R">RS Herbst</name>
</author>
<author><name sortKey="Soria, J C" uniqKey="Soria J">J-C Soria</name>
</author>
<author><name sortKey="Kowanetz, M" uniqKey="Kowanetz M">M Kowanetz</name>
</author>
<author><name sortKey="Fine, Gd" uniqKey="Fine G">GD Fine</name>
</author>
<author><name sortKey="Hamid, O" uniqKey="Hamid O">O Hamid</name>
</author>
<author><name sortKey="Gordon, Ms" uniqKey="Gordon M">MS Gordon</name>
</author>
<author><name sortKey="Sosman, Ja" uniqKey="Sosman J">JA Sosman</name>
</author>
<author><name sortKey="Mcdermott, Df" uniqKey="Mcdermott D">DF McDermott</name>
</author>
<author><name sortKey="Powderly, Jd" uniqKey="Powderly J">JD Powderly</name>
</author>
<author><name sortKey="Gettinger, Sn" uniqKey="Gettinger S">SN Gettinger</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Schmid, P" uniqKey="Schmid P">P Schmid</name>
</author>
<author><name sortKey="Adams, S" uniqKey="Adams S">S Adams</name>
</author>
<author><name sortKey="Rugo, Hs" uniqKey="Rugo H">HS Rugo</name>
</author>
<author><name sortKey="Schneeweiss, A" uniqKey="Schneeweiss A">A Schneeweiss</name>
</author>
<author><name sortKey="Barrios, Ch" uniqKey="Barrios C">CH Barrios</name>
</author>
<author><name sortKey="Iwata, H" uniqKey="Iwata H">H Iwata</name>
</author>
<author><name sortKey="Dieras, V" uniqKey="Dieras V">V Diéras</name>
</author>
<author><name sortKey="Hegg, R" uniqKey="Hegg R">R Hegg</name>
</author>
<author><name sortKey="Im, S A" uniqKey="Im S">S-A Im</name>
</author>
<author><name sortKey="Shaw Wright, G" uniqKey="Shaw Wright G">G Shaw Wright</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Emens, La" uniqKey="Emens L">LA Emens</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Antonia, Sj" uniqKey="Antonia S">SJ Antonia</name>
</author>
<author><name sortKey="Larkin, J" uniqKey="Larkin J">J Larkin</name>
</author>
<author><name sortKey="Ascierto, Pa" uniqKey="Ascierto P">PA Ascierto</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Terranova Barberio, M" uniqKey="Terranova Barberio M">M Terranova-Barberio</name>
</author>
<author><name sortKey="Thomas, S" uniqKey="Thomas S">S Thomas</name>
</author>
<author><name sortKey="Ali, N" uniqKey="Ali N">N Ali</name>
</author>
<author><name sortKey="Pawlowska, N" uniqKey="Pawlowska N">N Pawlowska</name>
</author>
<author><name sortKey="Park, J" uniqKey="Park J">J Park</name>
</author>
<author><name sortKey="Krings, G" uniqKey="Krings G">G Krings</name>
</author>
<author><name sortKey="Rosenblum, Md" uniqKey="Rosenblum M">MD Rosenblum</name>
</author>
<author><name sortKey="Budillon, A" uniqKey="Budillon A">A Budillon</name>
</author>
<author><name sortKey="Munster, Pn" uniqKey="Munster P">PN Munster</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Briere, D" uniqKey="Briere D">D Briere</name>
</author>
<author><name sortKey="Sudhakar, N" uniqKey="Sudhakar N">N Sudhakar</name>
</author>
<author><name sortKey="Woods, Dm" uniqKey="Woods D">DM Woods</name>
</author>
<author><name sortKey="Hallin, J" uniqKey="Hallin J">J Hallin</name>
</author>
<author><name sortKey="Engstrom, Ld" uniqKey="Engstrom L">LD Engstrom</name>
</author>
<author><name sortKey="Aranda, R" uniqKey="Aranda R">R Aranda</name>
</author>
<author><name sortKey="Chiang, H" uniqKey="Chiang H">H Chiang</name>
</author>
<author><name sortKey="Sodre, Al" uniqKey="Sodre A">AL Sodré</name>
</author>
<author><name sortKey="Olson, P" uniqKey="Olson P">P Olson</name>
</author>
<author><name sortKey="Weber, Js" uniqKey="Weber J">JS Weber</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Zhang, J" uniqKey="Zhang J">J Zhang</name>
</author>
<author><name sortKey="Bu, X" uniqKey="Bu X">X Bu</name>
</author>
<author><name sortKey="Wang, H" uniqKey="Wang H">H Wang</name>
</author>
<author><name sortKey="Zhu, Y" uniqKey="Zhu Y">Y Zhu</name>
</author>
<author><name sortKey="Geng, Y" uniqKey="Geng Y">Y Geng</name>
</author>
<author><name sortKey="Nihira, Nt" uniqKey="Nihira N">NT Nihira</name>
</author>
<author><name sortKey="Tan, Y" uniqKey="Tan Y">Y Tan</name>
</author>
<author><name sortKey="Ci, Y" uniqKey="Ci Y">Y Ci</name>
</author>
<author><name sortKey="Wu, F" uniqKey="Wu F">F Wu</name>
</author>
<author><name sortKey="Dai, X" uniqKey="Dai X">X Dai</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Slack Davis, Jk" uniqKey="Slack Davis J">JK Slack-Davis</name>
</author>
<author><name sortKey="Martin, Kh" uniqKey="Martin K">KH Martin</name>
</author>
<author><name sortKey="Tilghman, Rw" uniqKey="Tilghman R">RW Tilghman</name>
</author>
<author><name sortKey="Iwanicki, M" uniqKey="Iwanicki M">M Iwanicki</name>
</author>
<author><name sortKey="Ung, Ej" uniqKey="Ung E">EJ Ung</name>
</author>
<author><name sortKey="Autry, C" uniqKey="Autry C">C Autry</name>
</author>
<author><name sortKey="Luzzio, Mj" uniqKey="Luzzio M">MJ Luzzio</name>
</author>
<author><name sortKey="Cooper, B" uniqKey="Cooper B">B Cooper</name>
</author>
<author><name sortKey="Kath, Jc" uniqKey="Kath J">JC Kath</name>
</author>
<author><name sortKey="Roberts, Wg" uniqKey="Roberts W">WG Roberts</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Li, Cw" uniqKey="Li C">CW Li</name>
</author>
<author><name sortKey="Lim, So" uniqKey="Lim S">SO Lim</name>
</author>
<author><name sortKey="Chung, Em" uniqKey="Chung E">EM Chung</name>
</author>
<author><name sortKey="Kim, Ys" uniqKey="Kim Y">YS Kim</name>
</author>
<author><name sortKey="Park, Ah" uniqKey="Park A">AH Park</name>
</author>
<author><name sortKey="Yao, J" uniqKey="Yao J">J Yao</name>
</author>
<author><name sortKey="Cha, J H" uniqKey="Cha J">J-H Cha</name>
</author>
<author><name sortKey="Xia, W" uniqKey="Xia W">W Xia</name>
</author>
<author><name sortKey="Chan, L C" uniqKey="Chan L">L-C Chan</name>
</author>
<author><name sortKey="Kim, T" uniqKey="Kim T">T Kim</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Patel, Sp" uniqKey="Patel S">SP Patel</name>
</author>
<author><name sortKey="Kurzrock, R" uniqKey="Kurzrock R">R Kurzrock</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Lastwika, Kj" uniqKey="Lastwika K">KJ Lastwika</name>
</author>
<author><name sortKey="Wilson, W" uniqKey="Wilson W">W Wilson</name>
</author>
<author><name sortKey="Li, Qk" uniqKey="Li Q">QK Li</name>
</author>
<author><name sortKey="Norris, J" uniqKey="Norris J">J Norris</name>
</author>
<author><name sortKey="Xu, H" uniqKey="Xu H">H Xu</name>
</author>
<author><name sortKey="Ghazarian, Sr" uniqKey="Ghazarian S">SR Ghazarian</name>
</author>
<author><name sortKey="Kitagawa, H" uniqKey="Kitagawa H">H Kitagawa</name>
</author>
<author><name sortKey="Kawabata, S" uniqKey="Kawabata S">S Kawabata</name>
</author>
<author><name sortKey="Taube, Jm" uniqKey="Taube J">JM Taube</name>
</author>
<author><name sortKey="Yao, S" uniqKey="Yao S">S Yao</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Taube, Jm" uniqKey="Taube J">JM Taube</name>
</author>
<author><name sortKey="Anders, Ra" uniqKey="Anders R">RA Anders</name>
</author>
<author><name sortKey="Young, Gd" uniqKey="Young G">GD Young</name>
</author>
<author><name sortKey="Xu, H" uniqKey="Xu H">H Xu</name>
</author>
<author><name sortKey="Sharma, R" uniqKey="Sharma R">R Sharma</name>
</author>
<author><name sortKey="Mcmiller, Tl" uniqKey="Mcmiller T">TL McMiller</name>
</author>
<author><name sortKey="Chen, S" uniqKey="Chen S">S Chen</name>
</author>
<author><name sortKey="Klein, Ap" uniqKey="Klein A">AP Klein</name>
</author>
<author><name sortKey="Pardoll, Dm" uniqKey="Pardoll D">DM Pardoll</name>
</author>
<author><name sortKey="Topalian, Sl" uniqKey="Topalian S">SL Topalian</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Steeg, Ps" uniqKey="Steeg P">PS Steeg</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Yilmaz, M" uniqKey="Yilmaz M">M Yilmaz</name>
</author>
<author><name sortKey="Christofori, G" uniqKey="Christofori G">G Christofori</name>
</author>
<author><name sortKey="Lehembre, F" uniqKey="Lehembre F">F Lehembre</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Anders, Ck" uniqKey="Anders C">CK Anders</name>
</author>
<author><name sortKey="Carey, La" uniqKey="Carey L">LA Carey</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Hudis, Ca" uniqKey="Hudis C">CA Hudis</name>
</author>
<author><name sortKey="Gianni, L" uniqKey="Gianni L">L Gianni</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Wang, S" uniqKey="Wang S">S Wang</name>
</author>
<author><name sortKey="Li, J" uniqKey="Li J">J Li</name>
</author>
<author><name sortKey="Xie, J" uniqKey="Xie J">J Xie</name>
</author>
<author><name sortKey="Liu, F" uniqKey="Liu F">F Liu</name>
</author>
<author><name sortKey="Duan, Y" uniqKey="Duan Y">Y Duan</name>
</author>
<author><name sortKey="Wu, Y" uniqKey="Wu Y">Y Wu</name>
</author>
<author><name sortKey="Huang, S" uniqKey="Huang S">S Huang</name>
</author>
<author><name sortKey="He, X" uniqKey="He X">X He</name>
</author>
<author><name sortKey="Wang, Z" uniqKey="Wang Z">Z Wang</name>
</author>
<author><name sortKey="Wu, X" uniqKey="Wu X">X Wu</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Wang, Hb" uniqKey="Wang H">HB Wang</name>
</author>
<author><name sortKey="Yao, H" uniqKey="Yao H">H Yao</name>
</author>
<author><name sortKey="Li, Cs" uniqKey="Li C">CS Li</name>
</author>
<author><name sortKey="Liang, Lx" uniqKey="Liang L">LX Liang</name>
</author>
<author><name sortKey="Zhang, Y" uniqKey="Zhang Y">Y Zhang</name>
</author>
<author><name sortKey="Chen, Yx" uniqKey="Chen Y">YX Chen</name>
</author>
<author><name sortKey="Fang, Jy" uniqKey="Fang J">JY Fang</name>
</author>
<author><name sortKey="Xu, J" uniqKey="Xu J">J Xu</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Li, M" uniqKey="Li M">M Li</name>
</author>
<author><name sortKey="Li, A" uniqKey="Li A">A Li</name>
</author>
<author><name sortKey="Zhou, S" uniqKey="Zhou S">S Zhou</name>
</author>
<author><name sortKey="Xu, Y" uniqKey="Xu Y">Y Xu</name>
</author>
<author><name sortKey="Xiao, Y" uniqKey="Xiao Y">Y Xiao</name>
</author>
<author><name sortKey="Bi, R" uniqKey="Bi R">R Bi</name>
</author>
<author><name sortKey="Yang, W" uniqKey="Yang W">W Yang</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Stokes, Jb" uniqKey="Stokes J">JB Stokes</name>
</author>
<author><name sortKey="Adair, Sj" uniqKey="Adair S">SJ Adair</name>
</author>
<author><name sortKey="Slack Davis, Jk" uniqKey="Slack Davis J">JK Slack-Davis</name>
</author>
<author><name sortKey="Walters, Dm" uniqKey="Walters D">DM Walters</name>
</author>
<author><name sortKey="Tilghman, Rw" uniqKey="Tilghman R">RW Tilghman</name>
</author>
<author><name sortKey="Hershey, Ed" uniqKey="Hershey E">ED Hershey</name>
</author>
<author><name sortKey="Lowrey, B" uniqKey="Lowrey B">B Lowrey</name>
</author>
<author><name sortKey="Thomas, Ks" uniqKey="Thomas K">KS Thomas</name>
</author>
<author><name sortKey="Bouton, Ah" uniqKey="Bouton A">AH Bouton</name>
</author>
<author><name sortKey="Hwang, Rf" uniqKey="Hwang R">RF Hwang</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Endo, Y" uniqKey="Endo Y">Y Endo</name>
</author>
<author><name sortKey="Shen, Y" uniqKey="Shen Y">Y Shen</name>
</author>
<author><name sortKey="Youssef, La" uniqKey="Youssef L">LA Youssef</name>
</author>
<author><name sortKey="Mohan, N" uniqKey="Mohan N">N Mohan</name>
</author>
<author><name sortKey="Wu, Wj" uniqKey="Wu W">WJ Wu</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Mohan, N" uniqKey="Mohan N">N Mohan</name>
</author>
<author><name sortKey="Shen, Y" uniqKey="Shen Y">Y Shen</name>
</author>
<author><name sortKey="Dokmanovic, M" uniqKey="Dokmanovic M">M Dokmanovic</name>
</author>
<author><name sortKey="Endo, Y" uniqKey="Endo Y">Y Endo</name>
</author>
<author><name sortKey="Hirsch, Ds" uniqKey="Hirsch D">DS Hirsch</name>
</author>
<author><name sortKey="Wu, Wj" uniqKey="Wu W">WJ Wu</name>
</author>
</analytic>
</biblStruct>
</listBibl>
</div1>
</back>
</TEI>
<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Oncoimmunology</journal-id>
<journal-id journal-id-type="iso-abbrev">Oncoimmunology</journal-id>
<journal-id journal-id-type="publisher-id">KONI</journal-id>
<journal-id journal-id-type="publisher-id">koni20</journal-id>
<journal-title-group><journal-title>Oncoimmunology</journal-title>
</journal-title-group>
<issn pub-type="ppub">2162-4011</issn>
<issn pub-type="epub">2162-402X</issn>
<publisher><publisher-name>Taylor & Francis</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">31428520</article-id>
<article-id pub-id-type="pmc">6685513</article-id>
<article-id pub-id-type="publisher-id">1624128</article-id>
<article-id pub-id-type="doi">10.1080/2162402X.2019.1624128</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Original Research</subject>
</subj-group>
</article-categories>
<title-group><article-title>Atezolizumab potentiates Tcell-mediated cytotoxicity and coordinates with FAK to suppress cell invasion and motility in PD-L1<sup>+</sup>
triple negative breast cancer cells</article-title>
<alt-title alt-title-type="running-authors">N. MOHAN ET AL.</alt-title>
<alt-title alt-title-type="running-title">ONCOIMMUNOLOGY</alt-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Mohan</surname>
<given-names>Nishant</given-names>
</name>
<xref ref-type="aff" rid="AFF0001"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hosain</surname>
<given-names>Salman</given-names>
</name>
<xref ref-type="aff" rid="AFF0001"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Zhao</surname>
<given-names>Jun</given-names>
</name>
<xref ref-type="aff" rid="AFF0001"><sup>a</sup>
</xref>
<xref ref-type="aff" rid="AFF0002"><sup>b</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Shen</surname>
<given-names>Yi</given-names>
</name>
<xref ref-type="aff" rid="AFF0001"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Luo</surname>
<given-names>Xiao</given-names>
</name>
<xref ref-type="aff" rid="AFF0001"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Jiang</surname>
<given-names>Jiangsong</given-names>
</name>
<xref ref-type="aff" rid="AFF0001"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Endo</surname>
<given-names>Yukinori</given-names>
</name>
<xref ref-type="aff" rid="AFF0001"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author"><contrib-id contrib-id-type="orcid">http://orcid.org/0000-0001-5063-0957</contrib-id>
<name><surname>Wu</surname>
<given-names>Wen Jin</given-names>
</name>
<xref ref-type="corresp" rid="AN0001"></xref>
<xref ref-type="aff" rid="AFF0001"><sup>a</sup>
</xref>
</contrib>
<aff id="AFF0001"><label>a</label>
<institution>Division of Biotechnology Review and Research I, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration</institution>
, Silver Spring, Maryland,<country>USA</country>
</aff>
<aff id="AFF0002"><label>b</label>
<institution>Interagency Oncology Task Force (IOTF) Fellowship: Oncology Product Research/Review Fellow, National Cancer Institute</institution>
, Bethesda, Maryland,<country>USA</country>
</aff>
</contrib-group>
<author-notes><corresp id="AN0001">CONTACT Wen Jin Wu <email xlink:href="wen.wu@fda.hhs.gov">wen.wu@fda.hhs.gov</email>
<institution>Division of Biotechnology Review and Research I, Office of Biotechnology Products, OPQ-CDER-FDA</institution>
, <addr-line>HFD-123, Building 52/72, Room 2310, 10903 New Hampshire Avenue</addr-line>
, Silver Spring, Maryland 20993</corresp>
</author-notes>
<pub-date pub-type="collection"><year>2019</year>
</pub-date>
<pub-date pub-type="epub"><day>6</day>
<month>6</month>
<year>2019</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>6</day>
<month>6</month>
<year>2019</year>
</pub-date>
<pmc-comment> PMC Release delay is 0 months and 0 days and was based on the . </pmc-comment>
<volume>8</volume>
<issue>9</issue>
<elocation-id seq="6">e1624128</elocation-id>
<history><date date-type="received"><day>25</day>
<month>1</month>
<year>2019</year>
</date>
<date date-type="rev-recd"><day>17</day>
<month>5</month>
<year>2019</year>
</date>
<date date-type="accepted"><day>21</day>
<month>5</month>
<year>2019</year>
</date>
</history>
<permissions><copyright-statement>© 2019 The Author(s). Published with license by Taylor & Francis Group, LLC.</copyright-statement>
<copyright-year>2019</copyright-year>
<copyright-holder>The Author(s)</copyright-holder>
<license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc-nd/4.0/"><license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by-nc-nd/4.0/">http://creativecommons.org/licenses/by-nc-nd/4.0/</ext-link>
), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.</license-p>
</license>
</permissions>
<self-uri content-type="pdf" xlink:href="koni-08-09-1624128.pdf"></self-uri>
<abstract><title>ABSTRACT</title>
<p>Immune check point inhibitors targeting programmed cell death protein-1 (PD-1) and its ligand (PD-L1) have shown clinical success in treatment of human malignancies. Triple negative breast cancer (TNBC), which is primarily characterized by high heterogeneity and presence of tumor infiltrating lymphocytes, remains therapeutic challenge due to unavailability of approved targeted therapy. Therapeutic potential of immune check point inhibitors for TNBC patients is under active clinical investigation. In this study, we show that FDA-approved anti-PD-L1 antibody, atezolizumab (ATE), potentiates T cell-mediated cytotoxicity and apoptosis of TNBC cells that express higher levels of PD-L1, but does not have significant effect on TNBC cells expressing low levels of PD-L1. PD-L1 knockdown further confirmed that ability of ATE to promote T cell-induced cytotoxicity is PD-L1 expression dependent. Combination of ATE with PD-L1 upregulating agents, such as HDAC, proteasomal, and lysosomal inhibitors, further augmented cytotoxic activity of T cells toward TNBC cells. Based on analysis of breast cancer tissue samples deposited in The Cancer Genome Atlas (TCGA), we found a positive correlation between PD-L1 and focal adhesion kinase (FAK) mRNA expression in PD-L1-positive (PD-L1<sup>+</sup>
) TNBC, suggesting a functional association of FAK and immune checkpoints. We further demonstrate that ATE dramatically downregulates phosphorylation status of FAK, an important regulator of cell invasion and migration, and significantly enhances FAK inhibitor mediated inhibition of cell motility and invasion of PD-L1<sup>+</sup>
TNBC cells independent of T cells. Taken together, our data suggest that ATE shows promising anti-tumor activity in PD-L1<sup>+</sup>
TNBC via both T cell-dependent and -independent mechanisms.</p>
</abstract>
<kwd-group kwd-group-type="author"><title>KEYWORDS</title>
<kwd>atezolizumab</kwd>
<kwd>immune checkpoint inhibitors</kwd>
<kwd>triple negative breast cancer (TRBC)</kwd>
<kwd>PD-L1</kwd>
<kwd>focal adhesion kinase (FAK)</kwd>
</kwd-group>
<counts><fig-count count="6"></fig-count>
<ref-count count="39"></ref-count>
<page-count count="11"></page-count>
</counts>
</article-meta>
</front>
</pmc>
<affiliations><list><country><li>États-Unis</li>
</country>
</list>
<tree><country name="États-Unis"><noRegion><name sortKey="Mohan, Nishant" sort="Mohan, Nishant" uniqKey="Mohan N" first="Nishant" last="Mohan">Nishant Mohan</name>
</noRegion>
<name sortKey="Endo, Yukinori" sort="Endo, Yukinori" uniqKey="Endo Y" first="Yukinori" last="Endo">Yukinori Endo</name>
<name sortKey="Hosain, Salman" sort="Hosain, Salman" uniqKey="Hosain S" first="Salman" last="Hosain">Salman Hosain</name>
<name sortKey="Jiang, Jiangsong" sort="Jiang, Jiangsong" uniqKey="Jiang J" first="Jiangsong" last="Jiang">Jiangsong Jiang</name>
<name sortKey="Luo, Xiao" sort="Luo, Xiao" uniqKey="Luo X" first="Xiao" last="Luo">Xiao Luo</name>
<name sortKey="Shen, Yi" sort="Shen, Yi" uniqKey="Shen Y" first="Yi" last="Shen">Yi Shen</name>
<name sortKey="Wu, Wen Jin" sort="Wu, Wen Jin" uniqKey="Wu W" first="Wen Jin" last="Wu">Wen Jin Wu</name>
<name sortKey="Zhao, Jun" sort="Zhao, Jun" uniqKey="Zhao J" first="Jun" last="Zhao">Jun Zhao</name>
<name sortKey="Zhao, Jun" sort="Zhao, Jun" uniqKey="Zhao J" first="Jun" last="Zhao">Jun Zhao</name>
</country>
</tree>
</affiliations>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/ChloroquineV1/Data/Ncbi/Merge
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000941 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Ncbi/Merge/biblio.hfd -nk 000941 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Sante |area= ChloroquineV1 |flux= Ncbi |étape= Merge |type= RBID |clé= PMC:6685513 |texte= Atezolizumab potentiates Tcell-mediated cytotoxicity and coordinates with FAK to suppress cell invasion and motility in PD-L1+ triple negative breast cancer cells }}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Ncbi/Merge/RBID.i -Sk "pubmed:31428520" \ | HfdSelect -Kh $EXPLOR_AREA/Data/Ncbi/Merge/biblio.hfd \ | NlmPubMed2Wicri -a ChloroquineV1
![]() | This area was generated with Dilib version V0.6.33. | ![]() |