This paper investigates why sarcomatoid renal cell carcinoma (sRCC) is highly aggressive yet responds well to immune checkpoint blockade (ICB) therapy, a paradoxical clinical observation. Through single-cell and bulk transcriptomic analyses of over 3,000 tumors, the authors detail a robust anti-tumor immune microenvironment in sRCC characterized by activated and exhausted T cells, prevalent tertiary lymphoid structures (TLSs), and heightened B cell/humoral immune activity. Critically, the research yields a Genomic Dedifferentiation Signature (GDS) that is both negatively prognostic but positively predictive of ICB response, suggesting a biomarker for selecting patients most likely to benefit from immunotherapy.

References:

• Salgia N J, Khan A, Aubrecht W M, et al. Comprehensive tumor-immune profiling reveals mediators of paradoxical immune sensitivity in sarcomatoid renal cell carcinoma[J]. Cancer Cell, 2025.