肿瘤细胞治疗研究
英文原题：Skin-Resident γδ T Cells Mediate Potent and Selective Antitumor Cytotoxicity through Directed Chemotactic Migration and Mobilization of Cytotoxic Granules.
这些发现确立了DETCs作为多维抗肿瘤效应细胞，并为利用其独特生物学特性进行癌症免疫治疗提供了见解。
树突状表皮T细胞（DETCs）是主要定居于小鼠表皮的一类独特γδ T细胞亚群；然而，其抗肿瘤功能仍不明确。在本研究中，我们报道DETCs对多种肿瘤类型介导强效且高度选择性的细胞毒性，同时不损伤健康细胞。在体外，DETCs以剂量和时间依赖的方式诱导黑色素瘤、肝癌、结肠癌和淋巴瘤细胞系凋亡，且该过程需要直接的细胞间接触。在体内，过继转移DETCs显著抑制黑色素瘤生长和转移，同时延长生存期。在机制上，DETCs在识别肿瘤后上调穿孔素/颗粒酶B表达，抑制该通路可消除细胞毒性。DETCs在体内通过定向趋化和聚集选择性归巢至肿瘤细胞并与其形成紧密接触。肿瘤接触触发促炎性DETC活化，同时抑制微环境中的免疫抑制因子。值得注意的是，mTOR信号将肿瘤识别与DETC的运输、细胞毒性和炎症程序相偶联，因为雷帕霉素处理损害了效应功能和治疗疗效。总体而言，这些发现确立了DETCs作为多维抗肿瘤效应细胞，并为利用其独特生物学特性进行癌症免疫治疗提供了见解。
Dendritic epidermal T cells (DETCs) are a unique subset of γδ T cells that reside predominantly in mouse epidermis; yet, their antitumor functions remain enigmatic. In this study, we report that DETCs mediate potent and exquisitely selective cytotoxicity against diverse tumor types while sparing healthy cells. In vitro, DETCs induced apoptosis in melanoma, hepatoma, colon carcinoma, and lymphoma lines in a dose- and time-dependent manner that required direct cell-cell contact. In vivo, adoptive DETC transfer significantly suppressed melanoma growth and metastasis while prolonging survival. Mechanistically, DETCs upregulated perforin/granzyme B expression upon tumor recognition, and inhibition of this pathway ablated cytotoxicity. DETCs selectively homed to and formed intimate contacts with tumor cells in vivo through directed chemotaxis and aggregation. Tumor engagement triggered proinflammatory DETC activation while dampening immunosuppressive factors in the microenvironment. Notably, mTOR signaling coupled tumor recognition to DETC trafficking, cytotoxicity, and inflammatory programs because rapamycin treatment impaired effector functions and therapeutic efficacy. Collectively, these findings establish DETCs as multidimensional antitumor effectors and provide insights for harnessing their unique biology for cancer immunotherapy.
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