J Leukoc Biol. 2025 Aug 5;117(8):qiaf084. doi: 10.1093/jleuko/qiaf084.
ABSTRACT
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.
PMID:40853196 | DOI:10.1093/jleuko/qiaf084