Aptsiauri Natalia, Garrido Federico
Department of Biochemistry, Molecular Biology III and Immunology, University of Granada Medical School, Granada, Spain.
Institute of Biosanitary Research of Granada (IBS), Granada, Spain.
Clin Cancer Res. 2022 Dec 1;28(23):5021-5029. doi: 10.1158/1078-0432.CCR-21-3501.
HLA class I molecules are key in tumor recognition and T cell-mediated elimination. Loss of tumor HLA class I expression with different underlying molecular defects results in reduced antigen presentation and facilitates cancer immune evasion. It is also linked to significant changes in tumor microenvironment and tissue architecture. In this review, we summarize the current advances and future perspectives in the understanding of the mechanisms of MHC/HLA class I alterations during the natural history of tumor progression from a primary lesion to distant metastases. We also focus on recent clinical and experimental data demonstrating that lack of response to cancer immunotherapy frequently depends on the molecular nature of tumor HLA class I aberrations. Finally, we highlight the relevance of detecting and correcting the absence of tumor HLA expression to improve immunotherapy protocols.
HLA I类分子在肿瘤识别和T细胞介导的清除过程中起关键作用。具有不同潜在分子缺陷的肿瘤HLA I类表达缺失会导致抗原呈递减少，并促进癌症免疫逃逸。它还与肿瘤微环境和组织结构的显著变化有关。在本综述中，我们总结了在理解从原发性病变到远处转移的肿瘤进展自然史中MHC/HLA I类改变机制方面的当前进展和未来前景。我们还关注最近的临床和实验数据，这些数据表明对癌症免疫疗法缺乏反应通常取决于肿瘤HLA I类畸变的分子性质。最后，我们强调检测和纠正肿瘤HLA表达缺失以改进免疫治疗方案的相关性。
