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<p>The cellular mechanisms underlying HER2-positive gastric cancer (HER2<sup>+</sup> GC) responses to immunochemotherapy remain underexplored. Here, we perform longitudinal single-cell RNA-sequencing with paired TCR/BCR profiling on HER2<sup>+</sup> and HER2-negative gastric cancer (HER2<sup>−</sup> GC) pre- and post-treatment to find dynamic immune remodeling during. Pre-treatment HER2<sup>+</sup> GC displays an immunogenic microenvironment enriched with tumor-reactive T and B cells compared to HER2<sup>−</sup> GC. Following immunochemotherapy (anti-PD-1, XELOX/FOLFOX and anti-HER2), HER2<sup>+</sup> GC display clonal expansions of tumor-reactive T cells, increased memory B cell differentiation, enhanced naïve B cell recruitment, and enriched B-T cell interaction. Mechanistically, vitamin B5 promotes human T cell proliferation in coculture with naïve B cells. Notably, B5 biosynthesis is enriched in tumor-infiltrating naïve B cells in GC patient samples, and serum B5 concentration is elevated in the HER2<sup>+</sup>PD-L1<sup>+</sup> subset. In vivo, vitamin B5 supplementation boosts anti-PD-1 responses in female mice bearing subcutaneous cancers. Our data thus demonstrate a critical function for naïve B cells in immunochemotherapy response in HER2<sup>+</sup> GC, and also implicate vitamin B5 supplementation for potentiating immune checkpoint blockade.</p>

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Vitamin B5 supports anti-PD1 response in HER2-positive gastric cancer and enhances interaction between naïve B cells and T cells

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年8月5日

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  • Chaoye Wang,
  • Jing Yang,
  • Ming-Yu Lai,
  • Jia-Chen Lu,
  • Li-Qiong Yang,
  • Zhi-Ying Wu,
  • Hai-Yan Zhang,
  • Fang Wang,
  • Masami Yamamoto,
  • Tetsuya Tsukamoto,
  • Sachiyo Nomura,
  • Feng-Hua Wang,
  • Wen-Long Guan,
  • Ying Jin,
  • Rui-Hua Xu,
  • Qi Zhao,
  • Miao-Zhen Qiu

摘要

The cellular mechanisms underlying HER2-positive gastric cancer (HER2+ GC) responses to immunochemotherapy remain underexplored. Here, we perform longitudinal single-cell RNA-sequencing with paired TCR/BCR profiling on HER2+ and HER2-negative gastric cancer (HER2− GC) pre- and post-treatment to find dynamic immune remodeling during. Pre-treatment HER2+ GC displays an immunogenic microenvironment enriched with tumor-reactive T and B cells compared to HER2− GC. Following immunochemotherapy (anti-PD-1, XELOX/FOLFOX and anti-HER2), HER2+ GC display clonal expansions of tumor-reactive T cells, increased memory B cell differentiation, enhanced naïve B cell recruitment, and enriched B-T cell interaction. Mechanistically, vitamin B5 promotes human T cell proliferation in coculture with naïve B cells. Notably, B5 biosynthesis is enriched in tumor-infiltrating naïve B cells in GC patient samples, and serum B5 concentration is elevated in the HER2+PD-L1+ subset. In vivo, vitamin B5 supplementation boosts anti-PD-1 responses in female mice bearing subcutaneous cancers. Our data thus demonstrate a critical function for naïve B cells in immunochemotherapy response in HER2+ GC, and also implicate vitamin B5 supplementation for potentiating immune checkpoint blockade.