γδ T 细胞浸润到肿瘤中通常与患者预后的改善相关，但 γδ T 细胞的促肿瘤和杀肿瘤作用均已被记录。根据 T 细胞受体 (TCR) Vδ 的使用情况，人类 γδ T 细胞可分为功能不同的亚群。尽管如此，这些不同亚群对肿瘤免疫的贡献仍然难以捉摸。在这里，我们使用质量和流式细胞术、mRNA 定量和 TCR 测序提供了结肠肿瘤中详细的 γδ T 细胞分析。宏观上未受影响的结肠粘膜和肿瘤中 δ 链的使用情况在患者之间差异很大，其中有相当大比例的 Vδ1、Vδ2 和非 Vδ1 Vδ2 细胞。 Vδ 互补决定区 3 的测序表明，几乎所有非 Vδ1 Vδ2 细胞都使用 Vδ3，并且每个患者的肿瘤浸润 γδ 克隆型都是独特的。来自结肠肿瘤的非 Vδ1Vδ2 细胞表达多种激活标记物，但表达少量 NK 细胞受体和耗竭标记物。此外，mRNA 分析显示，非 Vδ1 Vδ2 细胞表达多种具有促肿瘤功能的蛋白质基因，例如中性粒细胞募集趋化因子、半乳糖凝集素 3 和转化生长因子-β 诱导的基因。总之，我们的结果显示各个肿瘤之间的 γδ T 细胞亚群存在很大差异，并且 Vδ3 细胞在结肠肿瘤中占 γδ T 细胞的很大比例。我们认为，结肠肿瘤中的个体 γδ T 细胞组成可能有助于有利和不利免疫反应之间的平衡，从而也有助于患者的治疗结果。© 2024。作者。

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.© 2024. The Author(s).