Overcoming acquired resistance to cancer immune checkpoint therapy: potential strategies based on molecular mechanisms

Cell & Bioscience

Review

Yin Han¹  Lingbin Meng²  Huanhuan Wang³  Jinlong Wei³  Xin Jiang³  Yuyu Zhang³  Bin Wang⁴  Qin Zhao⁵  Ying Xin⁶ 

[1] Cancer Prevention and Treatment Institute of Chengdu, Department of Pathology, Chengdu Fifth People’s Hospital (The Second Clinical Medical College, Affiliated Fifth People’s Hospital of Chengdu University of Traditional Chinese Medicine), 611137, Chengdu, China;Department of Hematology and Medical Oncology, Moffitt Cancer Center, 33612, Tampa, FL, USA;Department of Radiation Oncology, The First Hospital of Jilin University, 71 Xinmin Street, 130021, Changchun, China;Jilin Provincial Key Laboratory of Radiation Oncology & Therapy, The First Hospital of Jilin University, 130021, Changchun, China;NHC Key Laboratory of Radiobiology, School of Public Health, Jilin University, 130021, Changchun, China;Department of Radiation Oncology, The First Hospital of Jilin University, 71 Xinmin Street, 130021, Changchun, China;Medical Oncology, Cancer Center, West China Hospital, Sichuan University, 610041, Chengdu, China;Department of Radiation Oncology, The First Hospital of Jilin University, 71 Xinmin Street, 130021, Changchun, China;Medical Oncology, Cancer Center, West China Hospital, Sichuan University, 610041, Chengdu, China;Cancer Prevention and Treatment Institute of Chengdu, Department of Pathology, Chengdu Fifth People’s Hospital (The Second Clinical Medical College, Affiliated Fifth People’s Hospital of Chengdu University of Traditional Chinese Medicine), 611137, Chengdu, China;Key Laboratory of Pathobiology, Ministry of Education, Jilin University, 126 Xinmin Street, 130021, Changchun, China;

关键词: Immune checkpoint inhibitors;    Acquired resistance;    Mechanisms;    Tumor microenvironment;    Combination therapy;   

DOI  :  10.1186/s13578-023-01073-9

 received in 2022-07-23, accepted in 2023-06-15,  发布年份 2023

来源: Springer

【 摘 要 】

Immune checkpoint inhibitors (ICIs) targeting CTLA-4 and PD-1/PD-L1 to boost tumor-specific T lymphocyte immunity have opened up new avenues for the treatment of various histological types of malignancies, with the possibility of durable responses and improved survival. However, the development of acquired resistance to ICI therapy over time after an initial response remains a major obstacle in cancer therapeutics. The potential mechanisms of acquired resistance to ICI therapy are still ambiguous. In this review, we focused on the current understanding of the mechanisms of acquired resistance to ICIs, including the lack of neoantigens and effective antigen presentation, mutations of IFN‐γ/JAK signaling, and activation of alternate inhibitory immune checkpoints, immunosuppressive tumor microenvironment, epigenetic modification, and dysbiosis of the gut microbiome. Further, based on these mechanisms, potential therapeutic strategies to reverse the resistance to ICIs, which could provide clinical benefits to cancer patients, are also briefly discussed.

【 授权许可】

CC BY   
© The Author(s) 2023

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