A local human Vδ1 T cell population is associated with survival in nonsmall-cell lung cancer

Wu et al. utilize multiparametric analysis of early-stage human NSCLC to characterize a population of V delta 1 T cells displaying a resident memory and effector memory phenotype, which were associated with ongoing remission. Murine tissues harbor signature gamma delta T cell compartments with profound yet differential impacts on carcinogenesis. Conversely, human tissue-resident gamma delta cells are less well defined. In the present study, we show that human lung tissues harbor a resident V delta 1 gamma delta T cell population. Moreover, we demonstrate that V delta 1 T cells with resident memory and effector memory phenotypes were enriched in lung tumors compared with nontumor lung tissues. Intratumoral V delta 1 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 CD45RA(-)CD27(-) effector memory V delta 1 T cells in tumors and, most strikingly, with the numbers of CD103(+) tissue-resident V delta 1 T cells in nonmalignant lung tissues. Our findings offer basic insights into human body surface immunology that collectively support integrating V delta 1 T cell biology into immunotherapeutic strategies for nonsmall cell lung cancer.