γδ T-cell Receptors Derived from Breast Cancer-Infiltrating T Lymphocytes Mediate Antitumor Reactivity
γδ T-cell Receptors Derived from Breast Cancer-Infiltrating T Lymphocytes Mediate Antitumor Reactivity
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DOI：
10.1158/2326-6066.cir-19-0513
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发表时间：
2020-04-01
影响因子：
10.1
通讯作者：
Kuball, Jurgen
中科院分区：
文献类型：
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作者：
Janssen, Anke;Hidalgo, Jose Villacorta;Kuball, Jurgen
人实体瘤中的γ δ T细胞仍然不清楚。在这里，我们描述了分子和功能分析的T细胞受体（TCR）的肿瘤浸润性γ δ T淋巴细胞（γ δ TIL），直接接触肿瘤细胞在乳腺癌病变的档案材料。我们观察到大多数γ δ TIL具有促炎表型，只有少数与IL 17的表达相关。我们表征了γ δ TILs的TCR γ或TCR δ链，并观察到与其他肿瘤类型相比，V δ 2（+）T细胞的比例更高。通过重建来自单细胞测序的匹配的V δ 2（-）TCR γ和TCR δ对，我们的数据表明，gd TILs可能对乳腺癌和其他肿瘤类型有活性。对肿瘤细胞的反应模式依赖于TCR γ和TCR δ链，并且不依赖于通过其他先天免疫受体的额外共刺激。我们得出结论，γ δ TIL可以通过其单独的γ δ TCR对介导肿瘤反应性，并且表达源自γ δ TIL的TCR γ和δ链的工程化T细胞显示出针对不同癌细胞类型的有效抗肿瘤反应性，因此，可能是用于过继细胞疗法的工程化免疫细胞的有价值的工具。
gamma delta T cells in human solid tumors remain poorly defined. Here, we describe molecular and functional analyses of T-cell receptors (TCR) from tumor-infiltrating gamma delta T lymphocytes (gamma delta TIL) that were in direct contact with tumor cells in breast cancer lesions from archival material. We observed that the majority of gamma delta TILs harbored a proinflammatory phenotype and only a minority associated with the expression of IL17. We characterized TCR gamma or TCR delta chains of gamma delta TILs and observed a higher proportion of V delta 2(+) T cells compared with other tumor types. By reconstructing matched V delta 2(-) TCR gamma and TCR delta pairs derived from single-cell sequencing, our data suggest that gd TILs could be active against breast cancer and other tumor types. The reactivity pattern against tumor cells depended on both the TCR gamma and TCR delta chains and was independent of additional costimulation through other innate immune receptors. We conclude that gamma delta TILs can mediate tumor reactivity through their individual gamma delta TCR pairs and that engineered T cells expressing TCR gamma and delta chains derived from gamma delta 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.