免疫检查点抑制剂（ICI）是恢复抗肿瘤免疫力的癌症疗法；然而，只有一小部分患者仅通过 ICI 完全治愈。多种方法与其他方式相结合已被用来提高 ICI 治疗的疗效。在传统的癌症治疗中，放疗或基于 DNA 损伤的化疗是 ICI 的一个有前途的候选者，因为 DNA 损伤信号可能会刺激免疫活动，将肿瘤的免疫环境转变为热肿瘤。程序性死亡配体1（PD-L1）和人类白细胞抗原I类（HLA-I）作为免疫配体，调节肿瘤微环境中抗肿瘤免疫的平衡。 PD-L1 作为抑制细胞毒性 T 细胞活性的制动器，而 HLA-I 是促进 T 细胞信号传导下游的免疫加速器。越来越多的证据表明，DNA 损伤会增强 HLA-I 在受损细胞表面的表达。然而，尚不清楚 DNA 损伤细胞中的信号转导如何上调 HLA-I 与抗原的呈递。我们最近的研究揭示了 DNA 损伤诱导 HLA-I 呈递的机制，这需要通过首轮翻译进行多肽合成。在这篇综述中，我们总结了 HLA-I 提出的 DNA 损伤如何刺激抗原产生的最新概述。版权所有 © 2023 Elsevier B.V. 保留所有权利。

Immune checkpoint inhibitors (ICI) are cancer therapies that restore anti-tumor immunity; however, only a small percentage of patients have been completely cured by ICI alone. Multiple approaches in combination with other modalities have been used to improve the efficacy of ICI therapy. Among conventional cancer treatments, radiotherapy or DNA damage-based chemotherapy is a promising candidate as a partner of ICI because DNA damage signaling potentially stimulates immune activities turning the tumor's immune environment into hot tumors. Programmed death-ligand 1 (PD-L1) and human leukocyte antigen class I (HLA-I), which are immune ligands, regulate the balance of anti-tumor immunity in the tumor microenvironment. PD-L1 functions as a brake to suppress cytotoxic T cell activity, whereas HLA-I is an immune accelerator that promotes the downstream of the T cell signaling. Accumulating evidence has demonstrated that DNA damage enhances the presentation of HLA-I on the surface of damaged cells. However, it is unclear how signal transduction in DNA-damaged cells upregulates the presentation of HLA-I with antigens. Our recent study uncovered the mechanism underlying DNA damage-induced HLA-I presentation, which requires polypeptide synthesis through a pioneer round of translation. In this review, we summarize the latest overview of how DNA damage stimulates antigen production presented by HLA-I.Copyright © 2023 Elsevier B.V. All rights reserved.