Abstract
Purpose
As molecules responsible for presenting antigens to T lymphocytes, leukocytes antigens (HLAs) play a vital role in cancer immunology. This review aims to provide current understanding of HLAs in tumour immunology.
Methods
Perspectives on how HLA alterations may contribute to the immune escape of cancer cells and resistance to immunotherapy, and potential methods to overcome HLA defects were summarized. In addition, we discussed the potential association between HLA and immune-related adverse events (irAEs), which has not been reviewed elsewhere.
Results
Downregulation, loss of heterogeneity and entire loss of HLAs are responsible for the immune escape of tumour cells. The strategies to overcome the HLA defects can be effective therapies of cancer. Compared with classical HLA-I, non-classical HLA-I molecules, such as HLA-E and HLA-G, appear to be more reliable predictors of prognosis, as they tend to play immunosuppressive roles in antitumor response. Relative diversified or high expression of classical HLA-I are potential predictors of favourable response of immunotherapy. Certain HLA types may be associated to enhanced affinity to self-antigen-mimicked tumour-antigens, thus may positively correlated to irAEs triggered by checkpoint inhibitors.
Conclusions
Further studies exploring the relationship between HLAs and cancer may not only lead to the development of novel therapies but also bring about better management of irAEs.
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Data availability
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Funding program: Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (Construction and Application of Clinical Trial Institution Evaluation System 2021-I2M-1-045); Beijing Hope Run Special Fund of Cancer Foundation of China (LC2021B11).
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NJ and YY drafted the manuscript. DW, SW, YF, HM, PM and HH provided perspectives on HLA. MZ and YZ prepared the tables and figures. TY and NL supervised the study and reviewed and edited the manuscript.
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Min Zhang is employed by Novogene Co., Ltd, Beijing, China. Yu Zhang is employed by Renke Beijing Biotechnology Co., Ltd, Beijing, China. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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Jiang, N., Yu, Y., Wu, D. et al. HLA and tumour immunology: immune escape, immunotherapy and immune-related adverse events. J Cancer Res Clin Oncol 149, 737–747 (2023). https://doi.org/10.1007/s00432-022-04493-1
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DOI: https://doi.org/10.1007/s00432-022-04493-1