POU2F2 as a dual oncogenic and immunomodulatory driver in kidney renal clear cell carcinoma.

Kidney renal clear cell carcinoma (KIRC) features an immunosuppressive tumor microenvironment (TME). We investigated the role of transcription factor POU2F2 in KIRC oncogenesis and macrophage polarization. Single-cell and spatial transcriptomics showed that POU2F2 is upregulated in KIRC and associated with metastasis and poor prognosis. POU2F2 knockdown inhibited KIRC cell proliferation, migration, and invasion in vitro. POU2F2 expression correlated with macrophage infiltration and JAK-STAT signaling. Co-culture assays showed that POU2F2 silencing reduced macrophage recruitment and shifted M2 polarization toward an anti-tumor M1 phenotype. Overall, POU2F2 acts as an oncogenic driver and prognostic biomarker in KIRC, promoting an immunosuppressive TME and representing a potential therapeutic target.