Liu Yingting, Ma Jiajin, Xu Bin, Wu Yue, Xing Zhaoyu, Qian Heya, Chen Lujun, Zheng Xiao, Jiang Jingting
Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003, People's Republic of China.
Jiangsu Engineering Research Center for Tumor Immunotherapy, Changzhou, Jiangsu 213003, People's Republic of China.
J Leukoc Biol. 2025 Aug 5;117(8). doi: 10.1093/jleuko/qiaf084.
Tumor heterogeneity and the complex immune microenvironment make it challenging to identify candidates for immunotherapy using dominant biomarkers. Tumor-infiltrating CD8+T cells, particularly CD103+CD8+ tissue-resident T cells and their specific subsets, are generally linked to better outcomes in many cancers, but their role in renal cancer remains largely unexplored. Here, we report that tumor-infiltrating CD103+CD8+hnRNPA2B1+ tissue-resident T cells can serve as an unfavorable prognostic factor for ccRCC patients and may be related to PD-1 treatment outcomes. We assessed the infiltration of CD103+CD8+T, CD103+CD8+hnRNPA2B1+T and other CD8+T cell subsets in ccRCC using multiplex immunofluorescence staining, and evaluated their links to patient clinicopathological features and prognosis. With published single-cell data from ccRCC patients treated with PD-1 therapy, we studied the expression differences of hnRNPA2B1 in tumor-infiltrating CD8+ T cells between responders and nonresponders. Compared with adjacent normal tissues, the infiltration levels of CD103+CD8+T, CD103+CD8+hnRNPA2B1+T cells, and CD103+CD8+Bhlhe40+T cells in ccRCC tissues were all significantly higher (all P values were <0.01). Moreover, patients with a higher degree of infiltration of these cells had worse overall survival (HR = 0.3490, 95% CI: 0.09338 to 1.304, P = 0.0144). All of them can serve as independent prognostic factors for ccRCC patients (HR = 3.753, 95% CI: 1.317 to 10.693, P = 0.013). Single-cell transcriptomics revealed that tumor-infiltrating CD8+T cells in patients responding to PD-1 antibody treatment had higher hnRNPA2B1 expression compared with nonresponders. In summary, our study indicates that tumor-infiltrating CD103+CD8+hnRNPA2B1+ tissue-resident T cells can serve as predictive factors and indicators for unfavorable prognosis and patient responses to PD-1 treatment outcomes in ccRCC patients.
肿瘤异质性和复杂的免疫微环境使得利用主导生物标志物来识别免疫治疗候选者具有挑战性。肿瘤浸润性CD8 + T细胞，特别是CD103 + CD8 + 组织驻留T细胞及其特定亚群，在许多癌症中通常与更好的预后相关，但它们在肾癌中的作用仍 largely未被探索。在这里，我们报告肿瘤浸润性CD103 + CD8 + hnRNPA2B1 + 组织驻留T细胞可作为ccRCC患者的不良预后因素，并且可能与PD - 1治疗结果相关。我们使用多重免疫荧光染色评估了ccRCC中CD103 + CD8 + T、CD103 + CD8 + hnRNPA2B1 + T和其他CD8 + T细胞亚群的浸润情况，并评估了它们与患者临床病理特征和预后的联系。利用已发表的接受PD - 1治疗的ccRCC患者的单细胞数据，我们研究了应答者和非应答者之间肿瘤浸润性CD8 + T细胞中hnRNPA2B1的表达差异。与相邻正常组织相比，ccRCC组织中CD103 + CD8 + T、CD103 + CD8 + hnRNPA2B1 + T细胞和CD103 + CD8 + Bhlhe40 + T细胞的浸润水平均显著更高（所有P值均<0.01）。此外，这些细胞浸润程度较高的患者总生存期更差（HR = 0.3490，95% CI：0.09338至1.304，P = 0.0144）。所有这些均可作为ccRCC患者的独立预后因素（HR = 3.753，95% CI：1.317至10.693，P = 0.013）。单细胞转录组学显示，与非应答者相比，接受PD - 1抗体治疗的患者中肿瘤浸润性CD8 + T细胞具有更高的hnRNPA2B1表达。总之，我们的研究表明肿瘤浸润性CD103 + CD8 + hnRNPA2B1 + 组织驻留T细胞可作为ccRCC患者不良预后以及患者对PD - 1治疗结果反应的预测因素和指标。
