肿瘤浸润性 CD103+CD8+hnRNPA2B1+组织驻留 T 细胞提示透明细胞肾细胞癌患者预后不良

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.