SPP1+ Tumor-Associated Macrophages Drive Immunotherapy Resistance via CD8+ T-cell Dysfunction in Clear-Cell Renal Cell Carcinoma.

ABSTRACT: Tumor-associated macrophages (TAM) are key regulators of tumor immunity. With advances in single-cell analyses, secreted phosphoprotein 1 (SPP1)-positive TAMs have been observed across multiple tumor sites. However, their clinical relevance and phenotypic characteristics in clear-cell renal cell carcinoma (ccRCC) have not been comprehensively delineated. Using patient-level data from two in-house cohorts (n = 355), we explored the relationship between SPP1+ TAM infiltration and therapeutic response and prognosis in ccRCC. Four publicly available datasets consisting of 1,741 patients with ccRCC were included for external validation. Cytometry by time-of-flight and flow cytometry were utilized to phenotype SPP1+ TAMs and establish their impact on CD8+ T cells. Furthermore, we established an

SUBMITTER: Jiang W 

PROVIDER: S-EPMC12485372 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature