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

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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 that PIGR overexpression promotes tumor apoptosis and enhances immune responses, with these effects diminish in IgA-deficient mice. Elevated IgA and PIGR expression correlate with improved survival. These findings provide a single-cell atlas of the PSCC TME, highlighting the B cell–IgA–PIGR axis as a pivotal driver of antitumor immunity and clinical outcomes in HPV+ PSCC. The mechanisms underlying the improved survival in HPV-positive penile squamous cell carcinoma (PSCC) compared to HPV-negative counterparts remain to be explored. Here, single-cell sequencing highlights the role of the B cell-IgA-PIGR axis in enhancing antitumor immunity and improving clinical outcomes in HPV-positive PSCC.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.