肿瘤细胞治疗研究
英文原题：γδ T cell dichotomy with opposing cytotoxic and wound healing functions in human solid tumors.
γδ T细胞是重要的组织驻留固有T细胞，对组织稳态至关重要。
γδ T 细胞是重要的组织驻留固有 T 细胞，对组织稳态至关重要。γδ 细胞在大多数肿瘤中与良好预后相关；然而，对其在人类癌症中的异质性知之甚少。在此，我们对人类结直肠癌（CRC）和子宫内膜癌中的固有和适应性细胞进行了表型分析。我们发现，与正常组织相比，肿瘤中的 γδ 亚群和功能存在显著差异，且不同肿瘤类型中存在的 γδ 亚群也存在差异。在 CRC 中，出现了一个产生双调蛋白（AREG）的亚群，而子宫内膜癌则被细胞毒性细胞浸润。在人源化 CRC 模型中，肿瘤在过继转移后诱导 Vδ1 细胞出现这种 AREG 表型。为了利用 γδ 细胞在细胞治疗中的有益作用，我们开发了一种扩增方法，该方法增强了细胞毒性功能并提升了代谢灵活性，同时消除了 AREG 产生，实现了更强的肿瘤浸润和肿瘤清除。该方法作为“现货型”治疗选择，在细胞治疗中具有广泛的应用前景。
γδ T cells are important tissue-resident, innate T cells that are critical for tissue homeostasis. γδ cells are associated with positive prognosis in most tumors; however, little is known about their heterogeneity in human cancers. Here, we phenotyped innate and adaptive cells in human colorectal (CRC) and endometrial cancer. We found striking differences in γδ subsets and function in tumors compared to normal tissue, and in the γδ subsets present in tumor types. In CRC, an amphiregulin (AREG)-producing subset emerges, while endometrial cancer is infiltrated by cytotoxic cells. In humanized CRC models, tumors induced this AREG phenotype in Vδ1 cells after adoptive transfer. To exploit the beneficial roles of γδ cells for cell therapy, we developed an expansion method that enhanced cytotoxic function and boosted metabolic flexibility, while eliminating AREG production, achieving greater tumor infiltration and tumor clearance. This method has broad applications in cellular therapy as an 'off-the-shelf' treatment option.
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