Resistance Mechanism of PD-1/PD-L1 Blockade in the Cancer-Immunity Cycle
Identifieur interne : 000063 ( Main/Exploration ); précédent : 000062; suivant : 000064Resistance 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
Affiliations:
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<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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