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中华结直肠疾病电子杂志 ›› 2025, Vol. 14 ›› Issue (06) : 533 -537. doi: 10.3877/cma.j.issn.2095-3224.2025.06.007

论著

耗竭性CD8+T细胞表型对结直肠癌免疫检查点阻断剂疗效的影响
张金珠, 陈海鹏, 赵志勋, 王锡山()   
  1. 100021 北京,国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院结直肠外科
  • 收稿日期:2025-06-03 出版日期:2025-12-25
  • 通信作者: 王锡山
  • 基金资助:
    高端外国专家引进计划(No. G2023194001L); 北京市朝阳区科技计划(No. CYSF2223)

The impact of exhausted CD8+T cell phenotypes on the efficacy of immune checkpoint blockage in colorectal cancer

Jinzhu Zhang, Haipeng Chen, Zhixun Zhao, Xishan Wang()   

  1. Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
  • Received:2025-06-03 Published:2025-12-25
  • Corresponding author: Xishan Wang
引用本文:

张金珠, 陈海鹏, 赵志勋, 王锡山. 耗竭性CD8+T细胞表型对结直肠癌免疫检查点阻断剂疗效的影响[J/OL]. 中华结直肠疾病电子杂志, 2025, 14(06): 533-537.

Jinzhu Zhang, Haipeng Chen, Zhixun Zhao, Xishan Wang. The impact of exhausted CD8+T cell phenotypes on the efficacy of immune checkpoint blockage in colorectal cancer[J/OL]. Chinese Journal of Colorectal Diseases(Electronic Edition), 2025, 14(06): 533-537.

目的

探究免疫检查点抑制剂(ICB)治疗前肿瘤微环境中耗竭CD8+T细胞(CD8+Tex)表型特征与结直肠癌患者病理完全缓解的关系。

方法

利用公共单细胞数据库(GSE236581)中20例接受ICB治疗的结直肠癌患者治疗前肿瘤样本,分析耗竭性CD8+T细胞(CD8+Tex)亚群比例、终末耗竭评分、肿瘤特异性评分及T细胞受体(TCR)多样性在病理完全缓解和未完全缓解患者间的差异。

结果

病理完全缓解组CD8+Tex比例显著高于病理未完全缓解组(χ2=935.45,P<0.05);病理完全缓解组终末耗竭评分与肿瘤特异性评分均高于未完全缓解组(终末耗竭评分:t=7.53,P<0.05;肿瘤特异性评分:t=10.13,P<0.05),且该现象在dMMR和pMMR亚组中独立存在;病理完全缓解组CD8+Tex的TCR多样性高于病理未完全缓解组(t=3.65,P<0.05),且dMMR患者高于pMMR患者。

结论

治疗前肿瘤组织中高比例、高终末耗竭状态、高TCR多样性的CD8+Tex是预测ICB疗效的关键指标,其作用独立于MSI状态。该发现为拓展ICB治疗至pMMR患者提供了新依据。

Objective

To investigate the relationship between the phenotypic characteristics of CD8+ exhausted T cells (CD8+Tex) in the tumor microenvironment before immune checkpoint blockage (ICB) therapy and pathological complete response in colorectal cancer patients.

Methods

Tumor samples from 20 colorectal cancer patients treated with ICB before treatment were analyzed using public single-cell database (GSE236581). The proportion of CD8+Tex subgroups, terminal exhaustion scores, tumor-specific scores, and T cell receptor(TCR) diversity were compared between patients with pathological complete response and those without complete response.

Results

The proportion of CD8+Tex in the pathological complete response group was significantly higher than in the pathological non-complete response group (χ2=935.45, P<0.05). In addition, the terminal exhaustion score and tumor-specific score were higher in the pathological complete response group than in the non-complete response group (t=7.53, P<0.05; t=10.13, P<0.05), and this phenomenon was independently observed in both dMMR and pMMR subgroups. Lastly, the TCR diversity of CD8+Tex cells in the pathological complete response group was significantly higher (t=3.65, P<0.05), and dMMR patients had higher diversity than pMMR patients.

Conclusion

A high proportion, high terminal exhaustion status, and high TCR diversity of CD8+Tex cells in tumors before treatment are key markers for predicting ICB efficacy, independent of MSI status. This finding provides new evidence for extending ICB therapy to pMMR patients.

图1 大类细胞及CD8+T细胞的UMAP分群图。1A:结直肠肿瘤组织UMAP图;1B:大类细胞亚群marker热图;1C:CD8+T细胞UMAP图;1D:CD8+T细胞marker热图
表1 20例结直肠癌患者的基线资料[例(%)]
图2 病理完全缓解与未完全缓解结直肠癌的CD8+Tex细胞的功能评分差异。2A:病理完全缓解(CR)组与未完全缓解(NCR)组间CD8+Tex占所有CD8+T细胞比例差异;2B:CR组与NCR组间CD8+Tex终末耗竭评分差异;2C:CR组与NCR组间CD8+Tex肿瘤特异性评分差异;2D:dMMR患者中CR组与NCR组间CD8+Tex终末耗竭评分差异;2E:dMMR患者中CR组与NCR组间CD8+Tex肿瘤特异性评分差异;2F:pMMR患者中CR组与NCR组间CD8+Tex终末耗竭评分差异;2G:pMMR患者中CR组与NCR组间CD8+Tex肿瘤特异性评分差异;2H:CR组与NCR组间TCR多样性差异;2I:dMMR患者与pMMR患者间TCR多样性差异
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