Resistance Mechanism of PD-1/PD-L1 Blockade in the Cancer-Immunity Cycle
Identifieur interne : 000A84 ( Pmc/Curation ); précédent : 000A83; suivant : 000A85Resistance Mechanism of PD-1/PD-L1 Blockade in the Cancer-Immunity Cycle
Auteurs : Yuan Zhuang [République populaire de Chine] ; Chang Liu [République populaire de Chine] ; Jiaqing Liu [République populaire de Chine] ; Guang Li [République populaire de Chine]Source :
- OncoTargets and therapy [ 1178-6930 ] ; 2020.
Abstract
In recent years, the PD-1/PD-L1 axis blockade has become a very promising therapy with significant clinical benefits for multiple tumor types. However, some patients still do not respond sufficiently to PD-1/PD-L1 targeted monotherapy. Therefore, investigating the mechanism of PD-1 blockade resistance will assist in exploring new immunotherapy strategies, controlling the progress of the disease, and thus bringing more sustainable survival benefits to patients. The tumor-immune cycle is divided into the following seven steps: the release of cancer antigens, cancer antigen presentation, priming and activation, trafficking of T cells to tumors, infiltration of T cells into tumors, recognition of cancer cells by T cells, and killing of cancer cells. Given that PD-1/PD-L1 blockade is primarily involved in step 7, any abnormalities in the previous steps may affect the efficacy of PD-1/PD-L1 inhibitors and lead to drug resistance. This review discussed the resistance mechanisms of PD-1/PD-L1 blockade in each cancer-immunity step to finding a more suitable treatment population and an optimized combination therapy to exert immunotherapy in tumor treatment to a greater extent.
Url:
DOI: 10.2147/OTT.S239398
PubMed: 32021257
PubMed Central: 6954840
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<front><div type="abstract" xml:lang="en"><title>Abstract</title>
<p>In recent years, the PD-1/PD-L1 axis blockade has become a very promising therapy with significant clinical benefits for multiple tumor types. However, some patients still do not respond sufficiently to PD-1/PD-L1 targeted monotherapy. Therefore, investigating the mechanism of PD-1 blockade resistance will assist in exploring new immunotherapy strategies, controlling the progress of the disease, and thus bringing more sustainable survival benefits to patients. The tumor-immune cycle is divided into the following seven steps: the release of cancer antigens, cancer antigen presentation, priming and activation, trafficking of T cells to tumors, infiltration of T cells into tumors, recognition of cancer cells by T cells, and killing of cancer cells. Given that PD-1/PD-L1 blockade is primarily involved in step 7, any abnormalities in the previous steps may affect the efficacy of PD-1/PD-L1 inhibitors and lead to drug resistance. This review discussed the resistance mechanisms of PD-1/PD-L1 blockade in each cancer-immunity step to finding a more suitable treatment population and an optimized combination therapy to exert immunotherapy in tumor treatment to a greater extent.</p>
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<front><journal-meta><journal-id journal-id-type="nlm-ta">Onco Targets Ther</journal-id>
<journal-id journal-id-type="iso-abbrev">Onco Targets Ther</journal-id>
<journal-id journal-id-type="publisher-id">OTT</journal-id>
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<publisher><publisher-name>Dove</publisher-name>
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<article-categories><subj-group subj-group-type="heading"><subject>Review</subject>
</subj-group>
</article-categories>
<title-group><article-title>Resistance Mechanism of PD-1/PD-L1 Blockade in the Cancer-Immunity Cycle</article-title>
<alt-title alt-title-type="running-authors">Zhuang et al</alt-title>
<alt-title alt-title-type="running-title">Zhuang et al</alt-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Zhuang</surname>
<given-names>Yuan</given-names>
</name>
<xref ref-type="aff" rid="AFF0001">1</xref>
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<contrib contrib-type="author"><name><surname>Liu</surname>
<given-names>Chang</given-names>
</name>
<xref ref-type="aff" rid="AFF0001">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Liu</surname>
<given-names>Jiaqing</given-names>
</name>
<xref ref-type="aff" rid="AFF0001">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Li</surname>
<given-names>Guang</given-names>
</name>
<xref ref-type="corresp" rid="AN0001"></xref>
<xref ref-type="aff" rid="AFF0001">1</xref>
</contrib>
<aff id="AFF0001"><label>1</label>
<institution>Department of Radiation Oncology, The First Affiliated Hospital of China Medical University</institution>
,<addr-line>Shenyang</addr-line>
<addr-line>110001</addr-line>
,<addr-line>Liaoning</addr-line>
,<country>People’s Republic of China</country>
</aff>
</contrib-group>
<author-notes><corresp id="AN0001">Correspondence: Guang Li <institution>Department of Radiation Oncology, The First Hospital of China Medical University</institution>
, <addr-line>155 North Nanjing Street, Heping District</addr-line>
, <addr-line>Shenyang</addr-line>
, <addr-line>Liaoning</addr-line>
<addr-line>110001</addr-line>
, <country>People’s Republic of China</country>
<phone>Tel +86-13804058616</phone>
Email zyyannis0701@163.com</corresp>
</author-notes>
<pub-date pub-type="epub"><day>07</day>
<month>1</month>
<year>2020</year>
</pub-date>
<pub-date pub-type="collection"><year>2020</year>
</pub-date>
<volume>13</volume>
<fpage>83</fpage>
<lpage>94</lpage>
<history><date date-type="received"><day>20</day>
<month>11</month>
<year>2019</year>
</date>
<date date-type="accepted"><day>16</day>
<month>12</month>
<year>2019</year>
</date>
</history>
<permissions><copyright-statement>© 2020 Zhuang et al.</copyright-statement>
<copyright-year>2020</copyright-year>
<copyright-holder>Zhuang et al.</copyright-holder>
<license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc/3.0/"><license-p>This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at <ext-link ext-link-type="uri" xlink:href="https://www.dovepress.com/terms.php">https://www.dovepress.com/terms.php</ext-link>
and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by-nc/3.0/">http://creativecommons.org/licenses/by-nc/3.0/</ext-link>
). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (<ext-link ext-link-type="uri" xlink:href="https://www.dovepress.com/terms.php">https://www.dovepress.com/terms.php</ext-link>
).</license-p>
</license>
</permissions>
<abstract><title>Abstract</title>
<p>In recent years, the PD-1/PD-L1 axis blockade has become a very promising therapy with significant clinical benefits for multiple tumor types. However, some patients still do not respond sufficiently to PD-1/PD-L1 targeted monotherapy. Therefore, investigating the mechanism of PD-1 blockade resistance will assist in exploring new immunotherapy strategies, controlling the progress of the disease, and thus bringing more sustainable survival benefits to patients. The tumor-immune cycle is divided into the following seven steps: the release of cancer antigens, cancer antigen presentation, priming and activation, trafficking of T cells to tumors, infiltration of T cells into tumors, recognition of cancer cells by T cells, and killing of cancer cells. Given that PD-1/PD-L1 blockade is primarily involved in step 7, any abnormalities in the previous steps may affect the efficacy of PD-1/PD-L1 inhibitors and lead to drug resistance. This review discussed the resistance mechanisms of PD-1/PD-L1 blockade in each cancer-immunity step to finding a more suitable treatment population and an optimized combination therapy to exert immunotherapy in tumor treatment to a greater extent.</p>
</abstract>
<kwd-group kwd-group-type="author"><title>Keywords</title>
<kwd>immunotherapy</kwd>
<kwd>PD-1</kwd>
<kwd>PD-L1</kwd>
<kwd>resistance</kwd>
</kwd-group>
<counts><fig-count count="1"></fig-count>
<ref-count count="98"></ref-count>
<page-count count="12"></page-count>
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