肿瘤细胞治疗研究
英文原题：NKG2A expression identifies a subset of human Vδ2 T cells exerting the highest antitumor effector functions.
人Vδ2细胞是先天样γδ T效应细胞，对肿瘤发挥强效免疫监视作用。
人类Vδ2细胞是先天样γδ T效应细胞，对肿瘤执行强效免疫监视。NKG2A的组成性表达鉴定出Vδ2 T细胞的一个亚群，该亚群被赋予针对癌症的内在超反应性。事实上，NKG2A+和NKG2A-细胞的转录组谱刻画了Vδ2 T淋巴细胞的两个不同“谱系内”亚群，它们在发育早期即出现，保持其表型，并在成年生活中表现出自我更新能力。NKG2A+ Vδ2 T细胞的超反应性受到恶性细胞上表达的人类白细胞抗原E（HLA-E）所传递的抑制性信号的制衡，后者作为一种肿瘤逃逸机制。然而，无论是掩蔽还是敲除NKG2A，都能恢复Vδ2 T细胞发挥最高效应功能的能力，即使面对HLA-E+肿瘤也是如此。这在临床上高度相关，因为肝细胞癌、胶质母细胞瘤和非小细胞肺癌中NKG2A-HLA-E检查点参与程度的不同直接影响患者的总生存期。这些发现为开发细胞与免疫联合抗癌疗法开辟了道路。
Human Vδ2 cells are innate-like γδ T effectors performing potent immune surveillance against tumors. The constitutive expression of NKG2A identifies a subset of Vδ2 T cells licensed with an intrinsic hyper-responsiveness against cancer. Indeed, the transcriptomic profiles of NKG2A + and NKG2A - cells characterize two distinct "intralineages" of Vδ2 T lymphocytes that appear early during development, keep their phenotypes, and show self-renewal capabilities in adult life. The hyper-responsiveness of NKG2A + Vδ2 T cells is counterbalanced by the inhibitory signaling delivered by human leukocyte antigen E (HLA-E) expressed on malignant cells as a tumor-escape mechanism. However, either masking or knocking out NKG2A restores the capacity of Vδ2 T cells to exert the highest effector functions even against HLA-E + tumors. This is highly relevant in the clinic, as the different degrees of engagement of the NKG2A-HLA-E checkpoint in hepatocellular carcinoma, glioblastoma, and non-small cell lung cancer directly impact patients' overall survival. These findings open avenues for developing combined cellular and immunologic anticancer therapies.
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