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<p>The clinical response to immune checkpoint blockade (ICB) is limited in the majority of patients with colorectal cancer. These immune checkpoint proteins may not only inhibit T-cell-mediated antitumor immunity but also attenuate antigen presentation, including mutation-associated neoantigens. Here, we found that tumor B7-H3 levels may limit the therapeutic response to chemoradiotherapy in patients with locally-advanced rectal cancer. Knockdown of tumor B7-H3 significantly increased antigen presentation to increase T cell infiltration and killing ability, including neoantigen-specific T-cell response. Blockade of B7-H3 significantly augmented neoantigen-specific T cells response and remarkably enhanced the therapeutic efficacy of neoantigen-based cancer vaccines combined with radiotherapy, decreasing the risk of distant tumors in vivo. Taken together, these results demonstrated that targeting B7-H3 significantly enhanced the therapeutic efficacy of neoantigen cancer vaccines as well as radiotherapy by increasing the extent of neoantigen-specific T cells, even for PD-1/PD-L1 blockade-resistant colorectal cancers.</p>

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Targeting B7-H3 enhances the efficacy of neoantigen-based cancer vaccine in combination with radiotherapy

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月21日

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  • Tao-Wei Ke,
  • Chia-Yi Chen,
  • William Tzu-Liang Chen,
  • Yuan-Yao Tsai,
  • Shu-Fen Chiang,
  • Chi-Hsien Huang,
  • Yu-Sen Lin,
  • Te-Hong Chen,
  • Tsung-Wei Chen,
  • Ji-An Liang,
  • K. S. Clifford Chao,
  • Kevin Chih-Yang Huang

摘要

The clinical response to immune checkpoint blockade (ICB) is limited in the majority of patients with colorectal cancer. These immune checkpoint proteins may not only inhibit T-cell-mediated antitumor immunity but also attenuate antigen presentation, including mutation-associated neoantigens. Here, we found that tumor B7-H3 levels may limit the therapeutic response to chemoradiotherapy in patients with locally-advanced rectal cancer. Knockdown of tumor B7-H3 significantly increased antigen presentation to increase T cell infiltration and killing ability, including neoantigen-specific T-cell response. Blockade of B7-H3 significantly augmented neoantigen-specific T cells response and remarkably enhanced the therapeutic efficacy of neoantigen-based cancer vaccines combined with radiotherapy, decreasing the risk of distant tumors in vivo. Taken together, these results demonstrated that targeting B7-H3 significantly enhanced the therapeutic efficacy of neoantigen cancer vaccines as well as radiotherapy by increasing the extent of neoantigen-specific T cells, even for PD-1/PD-L1 blockade-resistant colorectal cancers.