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作者

Chenyue Zhang Chenxing Zhang Haiyong Wang

作者单位

Affiliations ¹ Department of Integrated Therapy, Fudan University Shanghai Cancer Center, Shanghai Medical College, Shanghai, China. ² Department of Nephrology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. ³ Department of Internal Medicine-Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China. Electronic address: wanghaiyong6688@12 com.

刊名

Cancer letters

年份

2023

卷号

Vol.562

页码

216182

ISSN

1872-7980

关键词

Clinical trials Combination therapy Host Immune checkpoint inhibitor resistance Tumor microenvironment.

摘要

Cancer treatment has been advanced with the advent of immune checkpoint inhibitors exemplified by anti-cytotoxic T-lymphocyte-associated protein 4 , anti-programmed cell death protein 1 and programmed cell death ligand 1 drugs. Patients have reaped substantial benefit from ICIs in many cancer types. However, few patients benefit from ICIs whereas the vast majority undergoing these treatments do not obtain survival benefit. Even for patients with initial responses, they may encounter drug resi...更多

Cancer treatment has been advanced with the advent of immune checkpoint inhibitors exemplified by anti-cytotoxic T-lymphocyte-associated protein 4 , anti-programmed cell death protein 1 and programmed cell death ligand 1 drugs. Patients have reaped substantial benefit from ICIs in many cancer types. However, few patients benefit from ICIs whereas the vast majority undergoing these treatments do not obtain survival benefit. Even for patients with initial responses, they may encounter drug resistance in their subsequent treatments, which limits the efficacy of ICIs. Therefore, a deepening understanding of drug resistance is critically important for the explorations of approaches to reverse drug resistance and to boost ICI efficacy. In the present review, different mechanisms of ICI resistance have been summarized according to the tumor intrinsic, tumor microenvironment and host classifications. We further elaborated corresponding strategies to battle against such resistance accordingly, which include targeting defects in antigen presentation, dysregulated interferon-γ signaling, neoantigen depletion, upregulation of other T cell checkpoints as well as immunosuppression and exclusion mediated by TME. Moreover, regarding the host, several additional approaches that interfere with diet and gut microbiome have also been described in reversing ICI resistance. Additionally, we provide an overall glimpse into the ongoing clinical trials that utilize these mechanisms to overcome ICI resistance. Finally, we summarize the challenges and opportunities that needs to be addressed in the investigation of ICI resistance mechanisms, with the aim to benefit more patients with cancer.收起

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