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.

中文翻译：

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癌症免疫治疗中 HLA I 类缺失的挑战：事实与希望

HLA I 类分子是肿瘤识别和 T 细胞介导的消除的关键。肿瘤 HLA I 类表达缺失以及不同的潜在分子缺陷会导致抗原呈递减少并促进癌症免疫逃避。它还与肿瘤微环境和组织结构的显着变化有关。在这篇综述中，我们总结了在肿瘤从原发灶进展到远处转移的自然史中 MHC/HLA I 类改变机制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，