Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
Nat Cancer. 2022 Jun;3(6):696-709. doi: 10.1038/s43018-022-00376-z. Epub 2022 May 30.
Murine tissues harbor signature γδ T cell compartments with profound yet differential impacts on carcinogenesis. Conversely, human tissue-resident γδ cells are less well defined. In the present study, we show that human lung tissues harbor a resident Vδ1 γδ T cell population. Moreover, we demonstrate that Vδ1 T cells with resident memory and effector memory phenotypes were enriched in lung tumors compared with nontumor lung tissues. Intratumoral Vδ1 T cells possessed stem-like features and were skewed toward cytolysis and helper T cell type 1 function, akin to intratumoral natural killer and CD8 T cells considered beneficial to the patient. Indeed, ongoing remission post-surgery was significantly associated with the numbers of CD45RACD27 effector memory Vδ1 T cells in tumors and, most strikingly, with the numbers of CD103 tissue-resident Vδ1 T cells in nonmalignant lung tissues. Our findings offer basic insights into human body surface immunology that collectively support integrating Vδ1 T cell biology into immunotherapeutic strategies for nonsmall cell lung cancer.
鼠类组织中存在特征性的 γδ T 细胞区室,对肿瘤发生具有深远而不同的影响。相反,人类组织驻留 γδ 细胞的特征还不太明确。在本研究中,我们表明人类肺部组织中存在驻留的 Vδ1 γδ T 细胞群体。此外,我们证明与非肿瘤肺部组织相比,肿瘤中富含具有驻留记忆和效应记忆表型的 Vδ1 T 细胞。肿瘤内 Vδ1 T 细胞具有干细胞样特征,并偏向细胞溶解和辅助性 T 细胞 1 型功能,类似于被认为对患者有益的肿瘤内自然杀伤细胞和 CD8 T 细胞。事实上,手术后持续缓解与肿瘤中 CD45RACD27 效应记忆 Vδ1 T 细胞的数量显著相关,与非恶性肺部组织中 CD103 组织驻留 Vδ1 T 细胞的数量最显著相关。我们的发现为人体表面免疫学提供了基本的见解,这些见解共同支持将 Vδ1 T 细胞生物学纳入非小细胞肺癌的免疫治疗策略。