Immunological profiling of molecularly classified high-risk endometrial cancers identifies POLE-mutant and microsatellite unstable carcinomas as candidates for checkpoint inhibition.
Identifieur interne : 000A24 ( PubMed/Checkpoint ); précédent : 000A23; suivant : 000A25Immunological profiling of molecularly classified high-risk endometrial cancers identifies POLE-mutant and microsatellite unstable carcinomas as candidates for checkpoint inhibition.
Auteurs : Florine A. Eggink [Pays-Bas] ; Inge C. Van Gool [Pays-Bas] ; Alexandra Leary [France] ; Pamela M. Pollock [Australie] ; Emma J. Crosbie [Royaume-Uni] ; Linda Mileshkin [Australie] ; Ekaterina S. Jordanova [Pays-Bas] ; Julien Adam [France] ; Luke Freeman-Mills [Royaume-Uni] ; David N. Church [Royaume-Uni] ; Carien L. Creutzberg [Pays-Bas] ; Marco De Bruyn [Pays-Bas] ; Hans W. Nijman [Pays-Bas] ; Tjalling Bosse [Pays-Bas]Source :
- Oncoimmunology [ 2162-4011 ] ; 2017.
Abstract
High-risk endometrial cancer (EC) is an aggressive disease for which new therapeutic options are needed. Aims of this study were to validate the enhanced immune response in highly mutated ECs and to explore immune profiles in other EC subgroups. We evaluated immune infiltration in 116 high-risk ECs from the TransPORTEC consortium, previously classified into four molecular subtypes: (i) ultramutated POLE exonuclease domain-mutant ECs (POLE-mutant); (ii) hypermutated microsatellite unstable (MSI); (iii) p53-mutant; and (iv) no specific molecular profile (NSMP). Within The Cancer Genome Atlas (TCGA) EC cohort, significantly higher numbers of predicted neoantigens were demonstrated in POLE-mutant and MSI tumors compared with NSMP and p53-mutants. This was reflected by enhanced immune expression and infiltration in POLE-mutant and MSI tumors in both the TCGA cohort (mRNA expression) and the TransPORTEC cohort (immunohistochemistry) with high infiltration of CD8(+) (90% and 69%), PD-1(+) (73% and 69%) and PD-L1(+) immune cells (100% and 71%). Notably, a subset of p53-mutant and NSMP cancers was characterized by signs of an antitumor immune response (43% and 31% of tumors with high infiltration of CD8(+) cells, respectively), despite a low number of predicted neoantigens. In conclusion, the presence of enhanced immune infiltration, particularly high numbers of PD-1 and PD-L1 positive cells, in highly mutated, neoantigen-rich POLE-mutant and MSI endometrial tumors suggests sensitivity to immune checkpoint inhibitors.
DOI: 10.1080/2162402X.2016.1264565
PubMed: 28344870
Affiliations:
- Australie, France, Pays-Bas, Royaume-Uni
- Angleterre, Grand Manchester, Groningue (province), Hollande-Méridionale, Hollande-Septentrionale, Oxfordshire
- Amsterdam, Groningue, Groningue (ville), Leyde, Manchester, Oxford
- Université d'Oxford, Université de Groningue, Université de Manchester
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Eggink</name><affiliation wicri:level="4"><nlm:affiliation>Department of Obstetrics and Gynecology, University of Groningen, University Medical Center Groningen , Groningen, the Netherlands.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Obstetrics and Gynecology, University of Groningen, University Medical Center Groningen , Groningen</wicri:regionArea><placeName><settlement type="city">Groningue</settlement><region nuts="2" type="province">Groningue (province)</region><settlement type="city">Groningue (ville)</settlement></placeName><orgName type="university">Université de Groningue</orgName></affiliation></author><author><name sortKey="Van Gool, Inge C" sort="Van Gool, Inge C" uniqKey="Van Gool I" first="Inge C" last="Van Gool">Inge C. 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Church</name><affiliation wicri:level="4"><nlm:affiliation>Tumour Genomics and Immunology Group, Oxford Centre for Cancer Gene Research, The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK; Oxford Cancer Centre, Churchill Hospital, Oxford, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Tumour Genomics and Immunology Group, Oxford Centre for Cancer Gene Research, The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK; Oxford Cancer Centre, Churchill Hospital, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region><settlement type="city">Oxford</settlement></placeName><orgName type="university">Université d'Oxford</orgName></affiliation></author><author><name sortKey="Creutzberg, Carien L" sort="Creutzberg, Carien L" uniqKey="Creutzberg C" first="Carien L" last="Creutzberg">Carien L. Creutzberg</name><affiliation wicri:level="3"><nlm:affiliation>Department of Clinical Oncology, Leiden University Medical Center , Leiden, the Netherlands.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Clinical Oncology, Leiden University Medical Center , Leiden</wicri:regionArea><placeName><settlement type="city">Leyde</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="De Bruyn, Marco" sort="De Bruyn, Marco" uniqKey="De Bruyn M" first="Marco" last="De Bruyn">Marco De Bruyn</name><affiliation wicri:level="4"><nlm:affiliation>Department of Obstetrics and Gynecology, University of Groningen, University Medical Center Groningen , Groningen, the Netherlands.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Obstetrics and Gynecology, University of Groningen, University Medical Center Groningen , Groningen</wicri:regionArea><placeName><settlement type="city">Groningue</settlement><region nuts="2" type="province">Groningue (province)</region><settlement type="city">Groningue (ville)</settlement></placeName><orgName type="university">Université de Groningue</orgName></affiliation></author><author><name sortKey="Nijman, Hans W" sort="Nijman, Hans W" uniqKey="Nijman H" first="Hans W" last="Nijman">Hans W. Nijman</name><affiliation wicri:level="4"><nlm:affiliation>Department of Obstetrics and Gynecology, University of Groningen, University Medical Center Groningen , Groningen, the Netherlands.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Obstetrics and Gynecology, University of Groningen, University Medical Center Groningen , Groningen</wicri:regionArea><placeName><settlement type="city">Groningue</settlement><region nuts="2" type="province">Groningue (province)</region><settlement type="city">Groningue (ville)</settlement></placeName><orgName type="university">Université de Groningue</orgName></affiliation></author><author><name sortKey="Bosse, Tjalling" sort="Bosse, Tjalling" uniqKey="Bosse T" first="Tjalling" last="Bosse">Tjalling Bosse</name><affiliation wicri:level="3"><nlm:affiliation>Department of Pathology, Leiden University Medical Center , Leiden, the Netherlands.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Pathology, Leiden University Medical Center , Leiden</wicri:regionArea><placeName><settlement type="city">Leyde</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2017">2017</date><idno type="RBID">pubmed:28344870</idno><idno type="pmid">28344870</idno><idno type="doi">10.1080/2162402X.2016.1264565</idno><idno type="wicri:Area/PubMed/Corpus">001470</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001470</idno><idno type="wicri:Area/PubMed/Curation">001448</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001448</idno><idno type="wicri:Area/PubMed/Checkpoint">001448</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">001448</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Immunological profiling of molecularly classified high-risk endometrial cancers identifies POLE-mutant and microsatellite unstable carcinomas as candidates for checkpoint inhibition.</title><author><name sortKey="Eggink, Florine A" sort="Eggink, Florine A" uniqKey="Eggink F" first="Florine A" last="Eggink">Florine A. Eggink</name><affiliation wicri:level="4"><nlm:affiliation>Department of Obstetrics and Gynecology, University of Groningen, University Medical Center Groningen , Groningen, the Netherlands.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Obstetrics and Gynecology, University of Groningen, University Medical Center Groningen , Groningen</wicri:regionArea><placeName><settlement type="city">Groningue</settlement><region nuts="2" type="province">Groningue (province)</region><settlement type="city">Groningue (ville)</settlement></placeName><orgName type="university">Université de Groningue</orgName></affiliation></author><author><name sortKey="Van Gool, Inge C" sort="Van Gool, Inge C" uniqKey="Van Gool I" first="Inge C" last="Van Gool">Inge C. Van Gool</name><affiliation wicri:level="3"><nlm:affiliation>Department of Pathology, Leiden University Medical Center , Leiden, the Netherlands.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Pathology, Leiden University Medical Center , Leiden</wicri:regionArea><placeName><settlement type="city">Leyde</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Leary, Alexandra" sort="Leary, Alexandra" uniqKey="Leary A" first="Alexandra" last="Leary">Alexandra Leary</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medical Oncology, INSERM U981, Gustave Roussy Cancer Center , Villejuif, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Medical Oncology, INSERM U981, Gustave Roussy Cancer Center , Villejuif</wicri:regionArea><wicri:noRegion>Villejuif</wicri:noRegion><wicri:noRegion>Villejuif</wicri:noRegion></affiliation></author><author><name sortKey="Pollock, Pamela M" sort="Pollock, Pamela M" uniqKey="Pollock P" first="Pamela M" last="Pollock">Pamela M. Pollock</name><affiliation wicri:level="1"><nlm:affiliation>Queensland University of Technology (QUT), Translational Research Institute , Brisbane, QLD, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Queensland University of Technology (QUT), Translational Research Institute , Brisbane, QLD</wicri:regionArea><wicri:noRegion>QLD</wicri:noRegion></affiliation></author><author><name sortKey="Crosbie, Emma J" sort="Crosbie, Emma J" uniqKey="Crosbie E" first="Emma J" last="Crosbie">Emma J. Crosbie</name><affiliation wicri:level="4"><nlm:affiliation>Institute of Cancer Sciences, University of Manchester, St Marys Hospital , Manchester, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Institute of Cancer Sciences, University of Manchester, St Marys Hospital , Manchester</wicri:regionArea><placeName><settlement type="city">Manchester</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Manchester</region><settlement type="city">Manchester</settlement></placeName><orgName type="university">Université de Manchester</orgName></affiliation></author><author><name sortKey="Mileshkin, Linda" sort="Mileshkin, Linda" uniqKey="Mileshkin L" first="Linda" last="Mileshkin">Linda Mileshkin</name><affiliation wicri:level="1"><nlm:affiliation>Division of Cancer Medicine, Peter MacCallum Cancer Centre , East Melbourne, VIC, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Division of Cancer Medicine, Peter MacCallum Cancer Centre , East Melbourne, VIC</wicri:regionArea><wicri:noRegion>VIC</wicri:noRegion></affiliation></author><author><name sortKey="Jordanova, Ekaterina S" sort="Jordanova, Ekaterina S" uniqKey="Jordanova E" first="Ekaterina S" last="Jordanova">Ekaterina S. Jordanova</name><affiliation wicri:level="3"><nlm:affiliation>Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands; Center for Gynecological Oncology Amsterdam, VU Medical Center, Amsterdam, the Netherlands.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands; Center for Gynecological Oncology Amsterdam, VU Medical Center, Amsterdam</wicri:regionArea><placeName><settlement type="city">Amsterdam</settlement><region nuts="2" type="province">Hollande-Septentrionale</region></placeName></affiliation></author><author><name sortKey="Adam, Julien" sort="Adam, Julien" uniqKey="Adam J" first="Julien" last="Adam">Julien Adam</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medical Oncology, INSERM U981, Gustave Roussy Cancer Center , Villejuif, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Medical Oncology, INSERM U981, Gustave Roussy Cancer Center , Villejuif</wicri:regionArea><wicri:noRegion>Villejuif</wicri:noRegion><wicri:noRegion>Villejuif</wicri:noRegion></affiliation></author><author><name sortKey="Freeman Mills, Luke" sort="Freeman Mills, Luke" uniqKey="Freeman Mills L" first="Luke" last="Freeman-Mills">Luke Freeman-Mills</name><affiliation wicri:level="3"><nlm:affiliation>Tumour Genomics and Immunology Group, Oxford Centre for Cancer Gene Research, The Wellcome Trust Centre for Human Genetics, University of Oxford , Oxford, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Tumour Genomics and Immunology Group, Oxford Centre for Cancer Gene Research, The Wellcome Trust Centre for Human Genetics, University of Oxford , Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region></placeName></affiliation></author><author><name sortKey="Church, David N" sort="Church, David N" uniqKey="Church D" first="David N" last="Church">David N. Church</name><affiliation wicri:level="4"><nlm:affiliation>Tumour Genomics and Immunology Group, Oxford Centre for Cancer Gene Research, The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK; Oxford Cancer Centre, Churchill Hospital, Oxford, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Tumour Genomics and Immunology Group, Oxford Centre for Cancer Gene Research, The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK; Oxford Cancer Centre, Churchill Hospital, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region><settlement type="city">Oxford</settlement></placeName><orgName type="university">Université d'Oxford</orgName></affiliation></author><author><name sortKey="Creutzberg, Carien L" sort="Creutzberg, Carien L" uniqKey="Creutzberg C" first="Carien L" last="Creutzberg">Carien L. Creutzberg</name><affiliation wicri:level="3"><nlm:affiliation>Department of Clinical Oncology, Leiden University Medical Center , Leiden, the Netherlands.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Clinical Oncology, Leiden University Medical Center , Leiden</wicri:regionArea><placeName><settlement type="city">Leyde</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="De Bruyn, Marco" sort="De Bruyn, Marco" uniqKey="De Bruyn M" first="Marco" last="De Bruyn">Marco De Bruyn</name><affiliation wicri:level="4"><nlm:affiliation>Department of Obstetrics and Gynecology, University of Groningen, University Medical Center Groningen , Groningen, the Netherlands.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Obstetrics and Gynecology, University of Groningen, University Medical Center Groningen , Groningen</wicri:regionArea><placeName><settlement type="city">Groningue</settlement><region nuts="2" type="province">Groningue (province)</region><settlement type="city">Groningue (ville)</settlement></placeName><orgName type="university">Université de Groningue</orgName></affiliation></author><author><name sortKey="Nijman, Hans W" sort="Nijman, Hans W" uniqKey="Nijman H" first="Hans W" last="Nijman">Hans W. Nijman</name><affiliation wicri:level="4"><nlm:affiliation>Department of Obstetrics and Gynecology, University of Groningen, University Medical Center Groningen , Groningen, the Netherlands.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Obstetrics and Gynecology, University of Groningen, University Medical Center Groningen , Groningen</wicri:regionArea><placeName><settlement type="city">Groningue</settlement><region nuts="2" type="province">Groningue (province)</region><settlement type="city">Groningue (ville)</settlement></placeName><orgName type="university">Université de Groningue</orgName></affiliation></author><author><name sortKey="Bosse, Tjalling" sort="Bosse, Tjalling" uniqKey="Bosse T" first="Tjalling" last="Bosse">Tjalling Bosse</name><affiliation wicri:level="3"><nlm:affiliation>Department of Pathology, Leiden University Medical Center , Leiden, the Netherlands.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Pathology, Leiden University Medical Center , Leiden</wicri:regionArea><placeName><settlement type="city">Leyde</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author></analytic><series><title level="j">Oncoimmunology</title><idno type="ISSN">2162-4011</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">High-risk endometrial cancer (EC) is an aggressive disease for which new therapeutic options are needed. Aims of this study were to validate the enhanced immune response in highly mutated ECs and to explore immune profiles in other EC subgroups. We evaluated immune infiltration in 116 high-risk ECs from the TransPORTEC consortium, previously classified into four molecular subtypes: (i) ultramutated POLE exonuclease domain-mutant ECs (POLE-mutant); (ii) hypermutated microsatellite unstable (MSI); (iii) p53-mutant; and (iv) no specific molecular profile (NSMP). Within The Cancer Genome Atlas (TCGA) EC cohort, significantly higher numbers of predicted neoantigens were demonstrated in POLE-mutant and MSI tumors compared with NSMP and p53-mutants. This was reflected by enhanced immune expression and infiltration in POLE-mutant and MSI tumors in both the TCGA cohort (mRNA expression) and the TransPORTEC cohort (immunohistochemistry) with high infiltration of CD8(+) (90% and 69%), PD-1(+) (73% and 69%) and PD-L1(+) immune cells (100% and 71%). Notably, a subset of p53-mutant and NSMP cancers was characterized by signs of an antitumor immune response (43% and 31% of tumors with high infiltration of CD8(+) cells, respectively), despite a low number of predicted neoantigens. In conclusion, the presence of enhanced immune infiltration, particularly high numbers of PD-1 and PD-L1 positive cells, in highly mutated, neoantigen-rich POLE-mutant and MSI endometrial tumors suggests sensitivity to immune checkpoint inhibitors.</div></front></TEI><pubmed><MedlineCitation Status="PubMed-not-MEDLINE" Owner="NLM"><PMID Version="1">28344870</PMID><DateCreated><Year>2017</Year><Month>03</Month><Day>27</Day></DateCreated><DateRevised><Year>2017</Year><Month>08</Month><Day>16</Day></DateRevised><Article PubModel="Electronic-eCollection"><Journal><ISSN IssnType="Print">2162-4011</ISSN><JournalIssue CitedMedium="Print"><Volume>6</Volume><Issue>2</Issue><PubDate><Year>2017</Year></PubDate></JournalIssue><Title>Oncoimmunology</Title><ISOAbbreviation>Oncoimmunology</ISOAbbreviation></Journal><ArticleTitle>Immunological profiling of molecularly classified high-risk endometrial cancers identifies POLE-mutant and microsatellite unstable carcinomas as candidates for checkpoint inhibition.</ArticleTitle><Pagination><MedlinePgn>e1264565</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1080/2162402X.2016.1264565</ELocationID><Abstract><AbstractText>High-risk endometrial cancer (EC) is an aggressive disease for which new therapeutic options are needed. Aims of this study were to validate the enhanced immune response in highly mutated ECs and to explore immune profiles in other EC subgroups. We evaluated immune infiltration in 116 high-risk ECs from the TransPORTEC consortium, previously classified into four molecular subtypes: (i) ultramutated POLE exonuclease domain-mutant ECs (POLE-mutant); (ii) hypermutated microsatellite unstable (MSI); (iii) p53-mutant; and (iv) no specific molecular profile (NSMP). Within The Cancer Genome Atlas (TCGA) EC cohort, significantly higher numbers of predicted neoantigens were demonstrated in POLE-mutant and MSI tumors compared with NSMP and p53-mutants. This was reflected by enhanced immune expression and infiltration in POLE-mutant and MSI tumors in both the TCGA cohort (mRNA expression) and the TransPORTEC cohort (immunohistochemistry) with high infiltration of CD8(+) (90% and 69%), PD-1(+) (73% and 69%) and PD-L1(+) immune cells (100% and 71%). Notably, a subset of p53-mutant and NSMP cancers was characterized by signs of an antitumor immune response (43% and 31% of tumors with high infiltration of CD8(+) cells, respectively), despite a low number of predicted neoantigens. In conclusion, the presence of enhanced immune infiltration, particularly high numbers of PD-1 and PD-L1 positive cells, in highly mutated, neoantigen-rich POLE-mutant and MSI endometrial tumors suggests sensitivity to immune checkpoint inhibitors.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Eggink</LastName><ForeName>Florine A</ForeName><Initials>FA</Initials><AffiliationInfo><Affiliation>Department of Obstetrics and Gynecology, University of Groningen, University Medical Center Groningen , Groningen, the Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Van Gool</LastName><ForeName>Inge C</ForeName><Initials>IC</Initials><AffiliationInfo><Affiliation>Department of Pathology, Leiden University Medical Center , Leiden, the Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Leary</LastName><ForeName>Alexandra</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Medical Oncology, INSERM U981, Gustave Roussy Cancer Center , Villejuif, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pollock</LastName><ForeName>Pamela M</ForeName><Initials>PM</Initials><AffiliationInfo><Affiliation>Queensland University of Technology (QUT), Translational Research Institute , Brisbane, QLD, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Crosbie</LastName><ForeName>Emma J</ForeName><Initials>EJ</Initials><AffiliationInfo><Affiliation>Institute of Cancer Sciences, University of Manchester, St Marys Hospital , Manchester, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mileshkin</LastName><ForeName>Linda</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Division of Cancer Medicine, Peter MacCallum Cancer Centre , East Melbourne, VIC, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jordanova</LastName><ForeName>Ekaterina S</ForeName><Initials>ES</Initials><AffiliationInfo><Affiliation>Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands; Center for Gynecological Oncology Amsterdam, VU Medical Center, Amsterdam, the Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Adam</LastName><ForeName>Julien</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Medical Oncology, INSERM U981, Gustave Roussy Cancer Center , Villejuif, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Freeman-Mills</LastName><ForeName>Luke</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Tumour Genomics and Immunology Group, Oxford Centre for Cancer Gene Research, The Wellcome Trust Centre for Human Genetics, University of Oxford , Oxford, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Church</LastName><ForeName>David N</ForeName><Initials>DN</Initials><AffiliationInfo><Affiliation>Tumour Genomics and Immunology Group, Oxford Centre for Cancer Gene Research, The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK; Oxford Cancer Centre, Churchill Hospital, Oxford, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Creutzberg</LastName><ForeName>Carien L</ForeName><Initials>CL</Initials><AffiliationInfo><Affiliation>Department of Clinical Oncology, Leiden University Medical Center , Leiden, the Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>De Bruyn</LastName><ForeName>Marco</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Obstetrics and Gynecology, University of Groningen, University Medical Center Groningen , Groningen, the Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nijman</LastName><ForeName>Hans W</ForeName><Initials>HW</Initials><AffiliationInfo><Affiliation>Department of Obstetrics and Gynecology, University of Groningen, University Medical Center Groningen , Groningen, the Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bosse</LastName><ForeName>Tjalling</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Department of Pathology, Leiden University Medical Center , Leiden, the Netherlands.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2016</Year><Month>12</Month><Day>09</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Oncoimmunology</MedlineTA><NlmUniqueID>101570526</NlmUniqueID><ISSNLinking>2162-4011</ISSNLinking></MedlineJournalInfo><CommentsCorrectionsList><CommentsCorrections RefType="Cites"><RefSource>N Engl J Med. 2015 Oct 22;373(17):1627-39</RefSource><PMID Version="1">26412456</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nature. 2014 Nov 27;515(7528):563-7</RefSource><PMID Version="1">25428504</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Clin Cancer Res. 2016 Jun 15;22(12):3005-15</RefSource><PMID Version="1">26763251</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Cell. 2016 Jul 28;166(3):755-65</RefSource><PMID Version="1">27372738</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Sci Transl Med. 2016 Mar 2;8(328):328rv4</RefSource><PMID Version="1">26936508</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>N Engl J Med. 2015 Nov 12;373(20):1984</RefSource><PMID Version="1">26559592</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Histopathology. 2016 May;68(6):916-24</RefSource><PMID Version="1">26416160</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nature. 2014 Nov 27;515(7528):568-71</RefSource><PMID Version="1">25428505</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Science. 2015 Apr 3;348(6230):124-8</RefSource><PMID Version="1">25765070</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Adv Immunol. 2016;130:95-190</RefSource><PMID Version="1">26923001</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Oncoimmunology. 2015 Aug 12;5(3):e1072675</RefSource><PMID Version="1">27141333</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Cancer Immunol Res. 2015 Jan;3(1):48-58</RefSource><PMID Version="1">25361854</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Int J Gynecol Cancer. 2016 Jun;26(5):933-8</RefSource><PMID Version="1">26937754</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>J Clin Oncol. 2016 Jul 1;34(19):2206-11</RefSource><PMID Version="1">27001570</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Immunol Rev. 2016 May;271(1):260-75</RefSource><PMID Version="1">27088920</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>J Clin Invest. 2016 Jun 1;126(6):2334-40</RefSource><PMID Version="1">27159395</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Clin Cancer Res. 2016 Jun 15;22(12):2865-73</RefSource><PMID Version="1">26763250</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nat Rev Cancer. 2016 Feb;16(2):71-81</RefSource><PMID Version="1">26822575</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Lancet Gastroenterol Hepatol. 2016 Nov;1(3):207-216</RefSource><PMID Version="1">28404093</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nature. 2012 Jul 18;487(7407):330-7</RefSource><PMID Version="1">22810696</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Clin Cancer Res. 2008 Apr 1;14(7):2028-35</RefSource><PMID Version="1">18381941</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Oncotarget. 2016 Jun 28;7(26):39885-39893</RefSource><PMID Version="1">27213585</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Front Immunol. 2015 Jan 22;6:1</RefSource><PMID Version="1">25657648</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Eur J Cancer. 2015 Feb;51(3):421-6</RefSource><PMID Version="1">25582496</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Clin Cancer Res. 2016 Dec 1;22(23 ):5682-5687</RefSource><PMID Version="1">27486176</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>JAMA Oncol. 2016 Jan;2(1):46-54</RefSource><PMID Version="1">26562159</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nat Rev Cancer. 2012 Mar 22;12(4):252-64</RefSource><PMID Version="1">22437870</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nat Med. 2003 May;9(5):562-7</RefSource><PMID Version="1">12704383</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>N Engl J Med. 2010 Aug 19;363(8):711-23</RefSource><PMID Version="1">20525992</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Cell. 2015 Jan 15;160(1-2):48-61</RefSource><PMID Version="1">25594174</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>J Exp Med. 2014 Oct 20;211(11):2231-48</RefSource><PMID Version="1">25245761</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>N Engl J Med. 2013 Jul 11;369(2):134-44</RefSource><PMID Version="1">23724846</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Exp Mol Pathol. 2013 Feb;94(1):121-5</RefSource><PMID Version="1">22750048</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Hum Mol Genet. 2013 Jul 15;22(14):2820-8</RefSource><PMID Version="1">23528559</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Immunity. 2016 Mar 15;44(3):698-711</RefSource><PMID Version="1">26982367</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Neuro Oncol. 2015 Oct;17 (10 ):1356-64</RefSource><PMID Version="1">25740784</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Eur J Cancer. 2016 Jun;60:1-11</RefSource><PMID Version="1">27038842</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>JAMA Oncol. 2015 Dec;1(9):1319-23</RefSource><PMID Version="1">26181000</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Mod Pathol. 2016 Feb;29(2):174-81</RefSource><PMID Version="1">26743472</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Mod Pathol. 2015 Jun;28(6):836-44</RefSource><PMID Version="1">25720322</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Front Immunol. 2015 Feb 23;6:67</RefSource><PMID Version="1">25755654</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nature. 2013 Aug 22;500(7463):415-21</RefSource><PMID Version="1">23945592</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Oncoimmunology. 2012 Nov 1;1(8):1281-1289</RefSource><PMID Version="1">23243591</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Clin Cancer Res. 2015 Jul 15;21(14):3347-55</RefSource><PMID Version="1">25878334</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>PLoS One. 2007 Aug 29;2(8):e796</RefSource><PMID Version="1">17726526</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nature. 2014 Nov 27;515(7528):558-62</RefSource><PMID Version="1">25428503</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Genome Res. 2014 May;24(5):743-50</RefSource><PMID Version="1">24782321</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>J Clin Oncol. 2013 Nov 10;31(32):e439-42</RefSource><PMID Version="1">24043743</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Gynecol Oncol. 2015 Jul;138(1):11-7</RefSource><PMID Version="1">25931171</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nature. 2013 May 2;497(7447):67-73</RefSource><PMID Version="1">23636398</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Genome Res. 2014 Nov;24(11):1740-50</RefSource><PMID Version="1">25228659</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Lancet Oncol. 2016 Aug;17(8):1114-26</RefSource><PMID Version="1">27397040</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Clin Cancer Res. 2014 Oct 1;20(19):5064-74</RefSource><PMID Version="1">24714771</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nat Med. 2016 Apr;22(4):433-8</RefSource><PMID Version="1">26901407</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Lancet Oncol. 2016 Jan;17(1):1</RefSource><PMID Version="1">26758748</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>N Engl J Med. 2014 Dec 4;371(23 ):2189-99</RefSource><PMID Version="1">25409260</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>N Engl J Med. 2015 Jun 25;372(26):2509-20</RefSource><PMID Version="1">26028255</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>J Natl Cancer Inst. 2014 Dec 12;107(1):402</RefSource><PMID Version="1">25505230</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nat Med. 2002 Aug;8(8):793-800</RefSource><PMID Version="1">12091876</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Cell Rep. 2016 Apr 14;:null</RefSource><PMID Version="1">27149842</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Cancer Treat Rev. 2016 Jul;48:61-8</RefSource><PMID Version="1">27362548</PMID></CommentsCorrections></CommentsCorrectionsList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Checkpoint inhibition</Keyword><Keyword MajorTopicYN="N">endometrial cancer</Keyword><Keyword MajorTopicYN="N">high-risk</Keyword><Keyword MajorTopicYN="N">molecular classification</Keyword><Keyword MajorTopicYN="N">tumor-infiltrating lymphocytes</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2016</Year><Month>10</Month><Day>12</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2016</Year><Month>11</Month><Day>16</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2016</Year><Month>11</Month><Day>17</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2017</Year><Month>3</Month><Day>28</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2017</Year><Month>3</Month><Day>28</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2017</Year><Month>3</Month><Day>28</Day><Hour>6</Hour><Minute>1</Minute></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">28344870</ArticleId><ArticleId IdType="doi">10.1080/2162402X.2016.1264565</ArticleId><ArticleId IdType="pii">1264565</ArticleId><ArticleId IdType="pmc">PMC5353925</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Australie</li><li>France</li><li>Pays-Bas</li><li>Royaume-Uni</li></country><region><li>Angleterre</li><li>Grand Manchester</li><li>Groningue (province)</li><li>Hollande-Méridionale</li><li>Hollande-Septentrionale</li><li>Oxfordshire</li></region><settlement><li>Amsterdam</li><li>Groningue</li><li>Groningue (ville)</li><li>Leyde</li><li>Manchester</li><li>Oxford</li></settlement><orgName><li>Université d'Oxford</li><li>Université de Groningue</li><li>Université de Manchester</li></orgName></list><tree><country name="Pays-Bas"><region name="Groningue (province)"><name sortKey="Eggink, Florine A" sort="Eggink, Florine A" uniqKey="Eggink F" first="Florine A" last="Eggink">Florine A. Eggink</name></region><name sortKey="Bosse, Tjalling" sort="Bosse, Tjalling" uniqKey="Bosse T" first="Tjalling" last="Bosse">Tjalling Bosse</name><name sortKey="Creutzberg, Carien L" sort="Creutzberg, Carien L" uniqKey="Creutzberg C" first="Carien L" last="Creutzberg">Carien L. Creutzberg</name><name sortKey="De Bruyn, Marco" sort="De Bruyn, Marco" uniqKey="De Bruyn M" first="Marco" last="De Bruyn">Marco De Bruyn</name><name sortKey="Jordanova, Ekaterina S" sort="Jordanova, Ekaterina S" uniqKey="Jordanova E" first="Ekaterina S" last="Jordanova">Ekaterina S. Jordanova</name><name sortKey="Nijman, Hans W" sort="Nijman, Hans W" uniqKey="Nijman H" first="Hans W" last="Nijman">Hans W. Nijman</name><name sortKey="Van Gool, Inge C" sort="Van Gool, Inge C" uniqKey="Van Gool I" first="Inge C" last="Van Gool">Inge C. Van Gool</name></country><country name="France"><noRegion><name sortKey="Leary, Alexandra" sort="Leary, Alexandra" uniqKey="Leary A" first="Alexandra" last="Leary">Alexandra Leary</name></noRegion><name sortKey="Adam, Julien" sort="Adam, Julien" uniqKey="Adam J" first="Julien" last="Adam">Julien Adam</name></country><country name="Australie"><noRegion><name sortKey="Pollock, Pamela M" sort="Pollock, Pamela M" uniqKey="Pollock P" first="Pamela M" last="Pollock">Pamela M. Pollock</name></noRegion><name sortKey="Mileshkin, Linda" sort="Mileshkin, Linda" uniqKey="Mileshkin L" first="Linda" last="Mileshkin">Linda Mileshkin</name></country><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Crosbie, Emma J" sort="Crosbie, Emma J" uniqKey="Crosbie E" first="Emma J" last="Crosbie">Emma J. Crosbie</name></region><name sortKey="Church, David N" sort="Church, David N" uniqKey="Church D" first="David N" last="Church">David N. 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