Work

Prognostic and immunobiological relevance of an onco-immune signature in clear cell renal cell carcinoma

Year: 2026

Type: article

Abstract: Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancer. Despite advances in anti-angiogenic and immune checkpoint therapy, accurate prognostic markers that run on archival tissue are still lacking. In this retrospective study, we quantified twelve onco-immune genes in FFPE tumor blocks from 88 ccRCC patients using the NanoString nCounter platform. A three-gene score (RORC, TGFB1, and SOCS1) was derived in TCGA-KIRC by Cox regression and evaluated in external bulk, single-cell, and spatial datasets. The twelve panel genes were profiled in the archival FFPE tumors, and the score was computed for every patient. In TCGA-KIRC, the score was associated with worse overall survival independently of stage, grade, age, and tumor purity (HR 1.57, 95% CI 1.28–1.92, p < 0.001), and its association with tumor grade was reproduced across external cohorts. Further, high-risk tumors were inflamed but immune-exhausted, with interferon and IL-6/JAK/STAT3 up-regulation, fibroblast and macrophage enrichment, and a lower predicted checkpoint-response rate. RORC was associated with a favorable metabolic module and TGFB1 with an adverse inflammatory-myeloid module, and interpretable machine learning supported the same directions. We identified a three-gene onco-immune score from an FFPE-compatible panel that is associated with survival independently of stage, grade, and age, and marks immunologically exhausted tumors. The score could assist risk stratification and support precision medicine in ccRCC.

Source: Clinical and Experimental Medicine

DOI: 10.1007/s10238-026-02312-2