A B cell-IgA-epithelial axis enhances antitumor immunity and improves outcome in HPV-associated penile squamous cell carcinoma.

ABSTRACT: Penile squamous cell carcinoma (PSCC) is a rare, aggressive malignancy, with HPV driving approximately 50% of cases and correlating with improved outcomes. In this study, we perform single-cell RNA sequencing on tumor microenvironment (TME) cells from 23 treatment-naive PSCC patients, including 11 cases reported previously, and validate our findings in a larger cohort of 85 patients. Our analysis reveals significant immune cell infiltration in PSCC, with HPV⁺ tumors exhibiting elevated levels of tumor-infiltrating B cells, plasma cells, tertiary lymphoid structures, and IgA secretion. A subset of malignant epithelial cells in HPV⁺ PSCC express the polymeric IgA receptor (PIGR), facilitating IgA transcytosis and inducing anti-tumor responses. Functional studies show th

SUBMITTER: Tao T 

PROVIDER: S-EPMC12816729 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature