Gamma Delta T-Cell Based Cancer Immunotherapy: Past-Present-Future.
Gamma Delta T-Cell Based Cancer Immunotherapy: Past-Present-Future.
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DOI：
10.3389/fimmu.2022.915837
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
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作者：
γδ T 细胞能够独立于 HLA 抗原呈递直接识别并杀死转化细胞，这使得它们成为癌症免疫治疗中非常有前景的效应细胞区室。正在开发基于 γδ T 细胞的新型免疫疗法，主要针对浸润肿瘤的两种主要 γδ T 细胞亚型（即 Vδ1 和 Vδ2）。 Vδ1 T 细胞亚群在组织中丰富，包含效应 T 细胞以及具有促肿瘤潜力的调节 T 细胞。相比之下，Vδ2 T 细胞在循环中富集，由大量相对同质的促炎效应 T 细胞亚群组成。健康个体的外周血中通常含有约 50-5 亿个 Vγ9Vδ2 T 细胞（占 CD3+ T 细胞总数的 1-10%），这些细胞在受到刺激后可以迅速扩增。 Vγ9Vδ2 T 细胞受体感知细胞内磷酸化代谢物，这些代谢物由于甲羟戊酸途径失调或药物干预而在癌细胞中积累。调查 Vγ9Vδ2 T 细胞治疗潜力的早期临床研究基于离体扩增和过继转移，或者使用氨基二磷酸盐或合成磷酸抗原（单独或与低剂量 IL-2 联合）进行全身激活。免疫相关不良事件（irAE）通常较轻微，但这些方法的临床疗效总体上带来的益处有限。近年来，重大进展再次让人们对 Vγ9Vδ2 T 细胞在癌症免疫治疗中的潜力感到兴奋。在这里，我们回顾了基于 γδ T 细胞的治疗策略，并讨论了目前在癌症患者临床研究中评估的前景，以及当前有希望的临床前结果可能产生的未来疗法。
γδ T-cells directly recognize and kill transformed cells independently of HLA-antigen presentation, which makes them a highly promising effector cell compartment for cancer immunotherapy. Novel γδ T-cell-based immunotherapies, primarily focusing on the two major γδ T-cell subtypes that infiltrate tumors (i.e. Vδ1 and Vδ2), are being developed. The Vδ1 T-cell subset is enriched in tissues and contains both effector T-cells as well as regulatory T-cells with tumor-promoting potential. Vδ2 T-cells, in contrast, are enriched in circulation and consist of a large, relatively homogeneous, pro-inflammatory effector T-cell subset. Healthy individuals typically harbor in the order of 50-500 million Vγ9Vδ2 T-cells in the peripheral blood alone (1-10% of the total CD3+ T-cell population), which can rapidly expand upon stimulation. The Vγ9Vδ2 T-cell receptor senses intracellular phosphorylated metabolites, which accumulate in cancer cells as a result of mevalonate pathway dysregulation or upon pharmaceutical intervention. Early clinical studies investigating the therapeutic potential of Vγ9Vδ2 T-cells were based on either ex vivo expansion and adoptive transfer or their systemic activation with aminobisphosphonates or synthetic phosphoantigens, either alone or combined with low dose IL-2. Immune-related adverse events (irAE) were generally \mild, but the clinical efficacy of these approaches provided overall limited benefit. In recent years, critical advances have renewed the excitement for the potential of Vγ9Vδ2 T-cells in cancer immunotherapy. Here, we review γδ T-cell-based therapeutic strategies and discuss the prospects of those currently evaluated in clinical studies in cancer patients as well as future therapies that might arise from current promising pre-clinical results.
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影响因子：
11.2
作者：
Dieli F;Vermijlen D;Fulfaro F;Caccamo N;Meraviglia S;Cicero G;Roberts A;Buccheri S;D'Asaro M;Gebbia N;Salerno A;Eberl M;Hayday AC
通讯作者：
Hayday AC
影响因子：
12.4
作者：
Deniger, Drew C.;Switzer, Kirsten;Cooper, Laurence J. N.
通讯作者：
Cooper, Laurence J. N.
影响因子：
168.9
作者：
Abramson, Jeremy S.;Palomba, M. Lia;Siddiqi, Tanya
通讯作者：
Siddiqi, Tanya
影响因子：
5.7
作者：
Ang, Wei Xia;Ng, Yu Yang;Wang, Shu
通讯作者：
Wang, Shu
影响因子：
7.3
作者：
Arbabi-Ghahroudi M
通讯作者：
Arbabi-Ghahroudi M