Laboratory of Translational Immunology, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands.
Institute of Immunology, Hannover Medical School, Hannover, Germany.
Nat Rev Drug Discov. 2020 Mar;19(3):169-184. doi: 10.1038/s41573-019-0038-z. Epub 2019 Sep 6.
Clinical responses to checkpoint inhibitors used for cancer immunotherapy seemingly require the presence of αβT cells that recognize tumour neoantigens, and are therefore primarily restricted to tumours with high mutational load. Approaches that could address this limitation by engineering αβT cells, such as chimeric antigen receptor T (CAR T) cells, are being investigated intensively, but these approaches have other issues, such as a scarcity of appropriate targets for CAR T cells in solid tumours. Consequently, there is renewed interest among translational researchers and commercial partners in the therapeutic use of γδT cells and their receptors. Overall, γδT cells display potent cytotoxicity, which usually does not depend on tumour-associated (neo)antigens, towards a large array of haematological and solid tumours, while preserving normal tissues. However, the precise mechanisms of tumour-specific γδT cells, as well as the mechanisms for self-recognition, remain poorly understood. In this Review, we discuss the challenges and opportunities for the clinical implementation of cancer immunotherapies based on γδT cells and their receptors.
临床对癌症免疫疗法中使用的检查点抑制剂的反应似乎需要识别肿瘤新抗原的 αβT 细胞的存在，因此主要局限于具有高突变负荷的肿瘤。通过工程化 αβT 细胞（例如嵌合抗原受体 T [CAR T] 细胞）来解决这一限制的方法正在被深入研究，但这些方法存在其他问题，例如 CAR T 细胞在实体瘤中缺乏合适的靶点。因此，转化研究人员和商业合作伙伴对 γδT 细胞及其受体的治疗用途重新产生了兴趣。总体而言，γδT 细胞对大量血液系统和实体瘤表现出强大的细胞毒性，通常不依赖于肿瘤相关（新）抗原，同时保留正常组织。然而，肿瘤特异性 γδT 细胞的精确机制以及自我识别的机制仍知之甚少。在这篇综述中，我们讨论了基于 γδT 细胞及其受体的癌症免疫疗法的临床实施所面临的挑战和机遇。
