γδ T cells in human solid tumors remain poorly defined. Here, we describe molecular and functional analyses of T-cell receptors (TCRs) from tumor-infiltrating γδ T lymphocytes (γδ TILs) that were in direct contact with tumor cells in breast cancer lesions from archival material. We observed that the majority of γδ TILs harbored a proinflammatory phenotype and only a minority associated with the expression of IL17. We characterized TCRγ or TCRδ chains of γδ TILs and observed a higher proportion of Vδ2+ T cells compared to other tumor types. By reconstructing matched Vδ2- TCRγ and TCRδ pairs derived from single-cell sequencing, our data suggest that γδ TILs could be active against breast cancer and other tumor types. The reactivity pattern against tumor cells depended on both the TCRγ and TCRδ chains and was independent of additional co-stimulation through other innate immune receptors. We conclude that γδ TILs can mediate tumor reactivity through their individual γδ TCR pairs and that engineered T cells expressing TCRγ and δ chains derived from γδ TILs display potent antitumor reactivity against different cancer cell types and, thus, may be a valuable tool for engineering immune cells for adoptive cell therapies.

中文翻译：

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源自乳腺癌浸润性T淋巴细胞的γδT细胞受体介导抗肿瘤反应性。

人实体瘤中的γδT细胞定义仍然不明确。在这里，我们描述了从肿瘤浸润性γδT淋巴细胞（γδTILs）的T细胞受体（TCRs）的分子和功能分析，这些淋巴细胞与档案材料中的乳腺癌病变中的肿瘤细胞直接接触。我们观察到，大多数γδTILs具有促炎表型，只有少数与IL17的表达有关。我们表征了γδTIL的TCRγ或TCRδ链，并观察到与其他肿瘤类型相比，Vδ2+ T细胞的比例更高。通过重建从单细胞测序获得的匹配的Vδ2-TCRγ和TCRδ对，我们的数据表明γδTILs可能对乳腺癌和其他类型的肿瘤具有活性。针对肿瘤细胞的反应模式取决于TCRγ和TCRδ链，并且不依赖于其他先天免疫受体的额外共同刺激。我们得出的结论是，γδTILs可以通过它们各自的γδTCR对介导肿瘤反应性，表达γδTILs的表达TCRγ和δ链的工程T细胞表现出对不同癌细胞类型的有效抗肿瘤反应性，因此，可能是工程免疫的有价值的工具用于过继细胞疗法的细胞。