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.

中文翻译：

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通过单细胞分析在大肠癌中T细胞的表型成型。

大多数具有微卫星稳定（MSS）大肠直肠癌（CRC）的患者无法从旨在挽救T细胞功能的免疫疗法中受益。因此，需要对CRC微环境中T细胞表型和功能状态有完整的了解。在这里，我们应用单细胞大规模流式细胞仪来塑造18例MSS CRC患者的T细胞表型，以更好地了解CRC作为一种全身性疾病，并寻找肿瘤驱动的T细胞谱变化。我们显示了T细胞亚群的患者间和患者内表型多样性。我们发现肿瘤病变处的免疫抑制/力竭性T细胞表型增加。增殖能力受损的CD8 + CD28-免疫衰老T细胞占主导地位。根据转录组和实时定量PCR分析，免疫抑制细胞的积累是由肿瘤微环境驱动的。早期和晚期患者之间的T细胞谱相似，这表明在CRC发生的早期就制定了免疫抑制微环境。T细胞浸润的定位和对其调节机制的了解可能会提供有价值的信息，以增强MSS CRC患者的免疫应答。