PDF(Pubmed)
Abstract：
TCRαβ+ CD4- CD8- double-negative T (DNT) cells are minor populations in peripheral blood, and their roles have mostly been discussed in inflammation and autoimmunity. However, the functions of DNT cells in tumor microenvironment remain to be elucidated. We investigated their characteristics, possible origins and functions in colorectal cancer tissues as well as their corresponding tumor-draining lymph nodes. We found a significant enrichment of DNT cells in tumor tissues compared with their corresponding lymph nodes, especially in tumors with lower T cell infiltration. T cell receptor (TCR) sequence analysis of CD4+ T, CD8+ T and DNT cells indicated that TCR sequences detected in DNT cells were found in CD8+ T cells, but rarely in CD4+ T cells, suggesting that a part of DNT cells was likely to be originated from CD8+ T cells. Through a single-cell transcriptomic analysis of DNT cells, we found that a DNT cell cluster, which showed similar phenotypes to central memory CD8+ T cells with low expression of effector and exhaustion markers, revealed some specific gene expression patterns, including higher GZMK expression. Moreover, in flow cytometry analysis, we found that DNT cells lost production of cytotoxic mediators. These findings imply that DNT cells might function as negative regulators of anti-tumor immune responses in tumor microenvironment.
摘要：
TCRαβ+CD4-CD8-双阴性T(DNT)细胞是外周血中的小群体,它们的作用主要在炎症和自身免疫中进行了讨论。然而,DNT细胞在肿瘤微环境中的功能仍有待阐明。我们调查了它们的特点,结直肠癌组织及其相应的肿瘤引流淋巴结的可能起源和功能。我们发现与相应的淋巴结相比，肿瘤组织中DNT细胞显著富集，尤其是T细胞浸润较低的肿瘤。CD4+T细胞受体(TCR)序列分析,CD8+T细胞和DNT细胞表明在DNT细胞中检测到的TCR序列在CD8+T细胞中发现，但很少在CD4+T细胞中，提示部分DNT细胞可能来源于CD8+T细胞。通过对DNT细胞的单细胞转录组学分析，我们发现了一个DNT细胞簇，它显示出与中枢记忆CD8+T细胞相似的表型，具有低表达的效应和耗尽标记，揭示了一些特定的基因表达模式，包括较高的GZMK表达。此外，在流式细胞术分析中，我们发现DNT细胞失去了细胞毒性介质的产生。这些发现暗示DNT细胞可能在肿瘤微环境中充当抗肿瘤免疫应答的负调节因子。
