γδ T cells impair airway macrophage differentiation in lung adenocarcinoma

Abstract

AbstractProtecting mucosal barriers, γδ T cells hold promise for the development of new cancer immunotherapies. In mice, γδ T cells can largely be segregated into CD27+and CD27−cells, and their functions are modulated by interactions with surrounding cells. However, which cells communicate directly with γδ T cells in lung adenocarcinoma remains unknown. To address this, we combined flow cytometry, confocal microscopy, and scRNA-seq, using an autochthonous genetically engineered mouse model and different γδ T cell-deficient settings. We found that γδ T cells were increased in tumour-bearing lungs, with an altered phenotype. CD27−and CD27+γδ T cells differed in their localisation and interactions including their tropism for macrophages. Overall, we propose a model where CD27+γδ T cells undermine the differentiation of tumour-associated macrophages into airway macrophages, fostering a negative outcome in lung adenocarcinoma. Determining its translatability to human health may offer new avenues for immunotherapeutic strategies.SummaryGuardians of pulmonary homeostasis, γδ T cells remain enigmatic regarding their role in lung adenocarcinoma. Raffo-Iraolagoitia et al. report that a subset of γδ T cells impairs the differentiation of tumour-associated macrophages into airway macrophages, relevant for the outcome of lung adenocarcinoma.Graphical Abstract