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Resistance Mechanism of PD-1/PD-L1 Blockade in the Cancer-Immunity Cycle

Identifieur interne : 000A84 ( Pmc/Curation ); précédent : 000A83; suivant : 000A85

Resistance 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 :

RBID : PMC:6954840

Abstract

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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<journal-id journal-id-type="iso-abbrev">Onco Targets Ther</journal-id>
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<surname>Li</surname>
<given-names>Guang</given-names>
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,
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,
<country>People’s Republic of China</country>
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<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>
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<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>
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<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>
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<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>
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<title>Keywords</title>
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