PDF(Pubmed)
Abstract：
Γδ T cell infiltration into tumours usually correlates with improved patient outcome, but both tumour-promoting and tumoricidal effects of γδ T cells have been documented. Human γδ T cells can be divided into functionally distinct subsets based on T cell receptor (TCR) Vδ usage. Still, the contribution of these different subsets to tumour immunity remains elusive. Here, we provide a detailed γδ T cell profiling in colon tumours, using mass and flow cytometry, mRNA quantification, and TCR sequencing. δ chain usage in both the macroscopically unaffected colon mucosa and tumours varied considerably between patients, with substantial fractions of Vδ1, Vδ2, and non-Vδ1 Vδ2 cells. Sequencing of the Vδ complementarity-determining region 3 showed that almost all non-Vδ1 Vδ2 cells used Vδ3 and that tumour-infiltrating γδ clonotypes were unique for every patient. Non-Vδ1Vδ2 cells from colon tumours expressed several activation markers but few NK cell receptors and exhaustion markers. In addition, mRNA analyses showed that non-Vδ1 Vδ2 cells expressed several genes for proteins with tumour-promoting functions, such as neutrophil-recruiting chemokines, Galectin 3, and transforming growth factor-beta induced. In summary, our results show a large variation in γδ T cell subsets between individual tumours, and that Vδ3 cells make up a substantial proportion of γδ T cells in colon tumours. We suggest that individual γδ T cell composition in colon tumours may contribute to the balance between favourable and adverse immune responses, and thereby also patient outcome.
摘要：
ΓδT细胞浸润肿瘤通常与改善患者预后相关，但是γδT细胞的促肿瘤作用和杀肿瘤作用都有文献记载。基于T细胞受体(TCR)Vδ的使用,人γδT细胞可分为功能上不同的亚群。尽管如此，这些不同的亚群对肿瘤免疫的贡献仍然难以捉摸。这里,我们提供了结肠肿瘤中详细的γδT细胞谱分析，使用质量和流式细胞术，mRNA定量，和TCR测序。患者之间宏观上不受影响的结肠粘膜和肿瘤中δ链的使用差异很大。大量的Vδ1，Vδ2和非Vδ1Vδ2细胞。Vδ互补决定区3的测序表明，几乎所有非Vδ1Vδ2细胞都使用Vδ3，并且肿瘤浸润性γδ克隆型对每个患者都是独特的。来自结肠肿瘤的非Vδ1Vδ2细胞表达了几种激活标记，但NK细胞受体和耗尽标记很少。此外,mRNA分析表明，非Vδ1Vδ2细胞表达了几种具有促进肿瘤功能的蛋白质基因，比如招募中性粒细胞的趋化因子，半乳糖凝集素3和转化生长因子-β诱导。总之,我们的结果表明，在单个肿瘤之间，γδT细胞亚群有很大的差异，在结肠肿瘤中，Vδ3细胞占γδT细胞的很大比例。我们建议结肠肿瘤中的单个γδT细胞组成可能有助于有利和不利的免疫反应之间的平衡。从而也是患者的结果。
