肿瘤细胞治疗研究
英文原题：Proteogenomic identification of an immunogenic antigen derived from human endogenous retrovirus in renal cell carcinoma.
Proteogenomic identification of an immunogenic antigen derived from human endogenous retrovirus in renal cell carcinoma.
CD8+ T 细胞能够识别由 HLA I 类分子呈递的肿瘤抗原并清除肿瘤细胞。
CD8⁺ T 细胞可识别由 HLA I 类分子呈递的肿瘤抗原并清除肿瘤细胞。尽管肾细胞癌（RCC）的肿瘤突变负荷较低，免疫检查点阻断（ICB）仍常使患者获益。本研究采用蛋白质基因组学方法，直接、全面地分析 RCC 组织中由 HLA I 类分子呈递的肽组，并发现免疫肽组中含有一小部分来源于人内源性逆转录病毒（hERV）的肽。通过比较肿瘤组织与正常肾组织，研究发现肿瘤相关 hERV 抗原，其中一种具有免疫原性，并可被宿主TIL（肿瘤浸润淋巴细胞）识别。使用 hERV 抗原刺激健康供者来源的外周血单个核细胞（PBMC），诱导产生了反应性 CD8⁺ T 细胞。这些结果表明，存在针对 hERV3895 抗原的抗肿瘤 CD8⁺ T 细胞免疫监视，并提示其在 RCC 患者中的潜在临床应用价值。
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.
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