CD8+ T细胞可以识别由HLA-I类分子展示的肿瘤抗原，并消灭肿瘤细胞。尽管其肿瘤突变负担较低，但免疫检查点阻断（ICB）常对肾细胞癌（RCC）患者有益。在这项利用蛋白质组基因组方法的研究中，我们直接且全面地探索了RCC组织中的HLA-I类呈递肽组，并证明其中含有一小部分来源于人内源性逆转录病毒（hERV）的肽段。肿瘤组织与正常肾组织的比较揭示了肿瘤相关的hERV抗原，其中一个抗原具有免疫原性，并被宿主肿瘤浸润淋巴细胞（TIL）所识别。hERV抗原的刺激可在健康供体来源的外周血单个核细胞（PBMC）中诱导活化的CD8+ T细胞。这些结果突显了针对hERV3895抗原的抗肿瘤CD8+ T细胞监视存在，并暗示其在RCC患者中的临床应用。

CD8+ T cells can recognize tumor antigens displayed by HLA class I molecules and eliminate tumor cells. Despite their low tumor mutation burden, immune checkpoint blockade (ICB) is often beneficial in patients with renal cell carcinoma (RCC). Here, using a proteogenomic approach, we directly and comprehensively explored the HLA class I-presenting peptidome of RCC tissues and demonstrated that the immunopeptidomes contain a small subset of peptides derived from human endogenous retroviruses (hERV). A comparison between tumor and normal kidney tissues revealed tumor-associated hERV antigens, one of which was immunogenic and recognized by host tumor-infiltrating lymphocytes (TIL). Stimulation with the hERV antigen induced reactive CD8+ T cells in healthy donor-derived (HD-derived) peripheral blood mononuclear cells (PBMC). These results highlight the presence of antitumor CD8+ T cell surveillance against hERV3895 antigens, suggesting their clinical applications in patients with RCC.