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<p>Colorectal cancer is a malignant disease with high morbidity and mortality. In recent years, immune checkpoint inhibitors have emerged as a promising therapeutic strategy; however, patients with proficient mismatch repair/microsatellite-stable (pMMR/MSS) colorectal cancer derive limited benefit from immunotherapy. We conducted a single-arm, exploratory clinical study to evaluate the efficacy of camrelizumab combined with apatinib in patients with advanced metastatic colorectal cancer who had received third-line or later treatment. This trial is registered with ClinicalTrials.gov (NCT04067986; registered August 20, 2019). Our results demonstrated that apatinib significantly enhanced the therapeutic efficacy of immunotherapy in patients with pMMR/MSS colorectal cancer. Mechanistically, apatinib improved immunotherapy outcomes by modulating the tumor microenvironment in vivo. Further in vitro experiments revealed that apatinib reduced levels of exosomal PD-L1 in the tumor microenvironment by inhibiting tumor-derived exosome secretion. This inhibitory effect was mediated through the regulation of Exo70. Collectively, our findings indicate that apatinib enhances the efficacy of camrelizumab in pMMR/MSS colorectal cancer and provide a theoretical rationale for the combined use of camrelizumab and apatinib in this patient population.</p>

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Apatinib enhances anti-PD-1 efficacy by inhibiting Exo70-mediated exosome secretion in pMMR/MSS colorectal cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月30日

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  • Lingying Zhao,
  • Chunyi Gao,
  • Xiaoxue Qiao,
  • Fanzhuoran Lou,
  • Bowen Zheng,
  • Miao Fu,
  • Xintian Huang,
  • Xiaowen Xie,
  • Wenqing Zhang,
  • Yongxiang Hong,
  • Kaiyi Rong,
  • Huibo Shi,
  • Li Xiao,
  • Tianhui Hu

摘要

Colorectal cancer is a malignant disease with high morbidity and mortality. In recent years, immune checkpoint inhibitors have emerged as a promising therapeutic strategy; however, patients with proficient mismatch repair/microsatellite-stable (pMMR/MSS) colorectal cancer derive limited benefit from immunotherapy. We conducted a single-arm, exploratory clinical study to evaluate the efficacy of camrelizumab combined with apatinib in patients with advanced metastatic colorectal cancer who had received third-line or later treatment. This trial is registered with ClinicalTrials.gov (NCT04067986; registered August 20, 2019). Our results demonstrated that apatinib significantly enhanced the therapeutic efficacy of immunotherapy in patients with pMMR/MSS colorectal cancer. Mechanistically, apatinib improved immunotherapy outcomes by modulating the tumor microenvironment in vivo. Further in vitro experiments revealed that apatinib reduced levels of exosomal PD-L1 in the tumor microenvironment by inhibiting tumor-derived exosome secretion. This inhibitory effect was mediated through the regulation of Exo70. Collectively, our findings indicate that apatinib enhances the efficacy of camrelizumab in pMMR/MSS colorectal cancer and provide a theoretical rationale for the combined use of camrelizumab and apatinib in this patient population.