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

doi:10.3877/cma.j.issn.2095-3224.2025.06.007

Abstract

Abstract:

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.

Key words: Colorectal cancer, Immune checkpoint inhibitors, CD8⁺T cell phenotype

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]. Chinese Journal of Colorectal Diseases(Electronic Edition), 2025, 14(06): 533-537.

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URL: https://zhjzcjbdzzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.2095-3224.2025.06.007

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Figures/Tables 3

References 20

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基线资料	数值
性别
男性	17（85.0）
女性	3（15.0）
年龄（岁）
>60	5（25.0）
≤60	15（75.0）
肿瘤部位
直肠	6（30.0）
结肠	14（70.0）
TNM分期
Ⅰ	0
Ⅱ	2（10.0）
Ⅲ	15（75.0）
Ⅳ	3（15.0）
微卫星状态
dMMR	14（70.0）
pMMR	6（30.0）
治疗反应
完全缓解	11（55.0）
部分缓解	6（30.0）
疾病稳定	3（15.0）
ICB药物
卡瑞利珠单抗	1（5.0）
帕博利珠单抗	12（60.0）
信迪利单抗	7（35.0）
治疗方案
单免治疗	16（80.0）
单免治疗+化疗	4（20.0）

基线资料	数值
性别
男性	17（85.0）
女性	3（15.0）
年龄（岁）
>60	5（25.0）
≤60	15（75.0）
肿瘤部位
直肠	6（30.0）
结肠	14（70.0）
TNM分期
Ⅰ	0
Ⅱ	2（10.0）
Ⅲ	15（75.0）
Ⅳ	3（15.0）
微卫星状态
dMMR	14（70.0）
pMMR	6（30.0）
治疗反应
完全缓解	11（55.0）
部分缓解	6（30.0）
疾病稳定	3（15.0）
ICB药物
卡瑞利珠单抗	1（5.0）
帕博利珠单抗	12（60.0）
信迪利单抗	7（35.0）
治疗方案
单免治疗	16（80.0）
单免治疗+化疗	4（20.0）

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