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<p>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<sup>+</sup> 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<sup>+</sup> 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<sup>+</sup> PSCC.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月11日

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  • Tao Tao,
  • Lianbang Zhu,
  • Deyun Shen,
  • Jiayang Zhang,
  • Panrui Zhang,
  • Zhixi Gu,
  • Dan Cao,
  • Jun Xiao,
  • Wen Pan

摘要

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.