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0This study presents a comprehensive single-cell transcriptomic atlas of the advanced renal cell carcinoma (aRCC) tumor microenvironment to uncover mechanisms of drug resistance. By analyzing 61 tumor samples, researchers identified a specific SAA–CEACAM1–TIM-3 axis that drives therapeutic failure by fostering an immunosuppressive niche. The findings highlight that SAA+ tumor cells recruit a unique subset of VEGFA+ neutrophils, which express CEACAM1 to impair the cytotoxic function of CD8+ T cells. Preclinical evidence suggests that targeting this axis through SAA inhibition or CEACAM1–TIM-3 blockade can successfully reinvigorate the immune response and enhance the efficacy of combination therapies. Ultimately, this research identifies circulating SAA as a potential biomarker and offers new strategies for overcoming immunotherapy resistance in kidney cancer.
References:
Gu L, Zhang Q, Liang Q, et al. PD-1 blockade plus tyrosine kinase inhibitor remodels the tumor microenvironment in advanced renal cell carcinoma[J]. Nature Communications, 2026, 17(1): 4626.
