Phenotype molding of T cells in colorectal cancer by single-cell analysis

被引:29
|
作者
Di, Jiabo [1 ]
Liu, Maoxing [1 ]
Fan, Yingcong [1 ]
Gao, Pin [1 ]
Wang, Zaozao [1 ]
Jiang, Beihai [1 ]
Su, Xiangqian [1 ]
机构
[1] Peking Univ, Dept Gastrointestinal Surg 4, Minist Educ, Key Lab Carcinogenesis & Translat Res,Canc Hosp &, Beijing, Peoples R China
基金
北京市自然科学基金; 中国国家自然科学基金;
关键词
colorectal cancer; T-cell phenotype; single-cell mass cytometry; immunosuppression; T-cell exhaustion; REGULATORY CELLS; LUNG-CANCER; IMMUNITY; LYMPHOCYTES; METASTASIS; PROMOTES; EXPANSION; THERAPY; SUBSET; CTLA-4;
D O I
10.1002/ijc.32856
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The majority of patients with microsatellite stable (MSS) colorectal cancer (CRC) do not benefit from the immunotherapies directed at rescuing T-cell functions. Therefore, complete understanding of T-cell phenotypes and functional status in the CRC microenvironment is desirable. Here, we applied single-cell mass cytometry to mold the T-cell phenotype in 18 patients with MSS CRC for better understanding of CRC as a systemic disease and to search for tumor-driven T-cell profile changes. We show interpatient and intrapatient phenotypic diversity of T-cell subsets. We revealed increased immunosuppressive/exhausted T-cell phenotypes at tumor lesions. CD8+ CD28- immunosenescent T cells with impaired proliferation capacity dominate the T-cell compartment. As per the transcriptome and quantitative real time-PCR analysis, the accumulation of immunosuppressive cells is driven by the tumor microenvironment. T-cell profiles are similar between patients at early and late stages, indicating that the immunosuppressive microenvironment is formulated early during CRC development. Mapping of T-cell infiltration and understanding of the mechanisms underlying their regulation may provide valuable information to boost the immune response in patients with MSS CRC.
引用
收藏
页码:2281 / 2295
页数:15
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