γδ T cells impair airway macrophage differentiation in lung adenocarcinoma

Protecting mucosal barriers, {gamma}{delta} T cells hold promise for the development of new cancer immunotherapies. In mice, {gamma}{delta} 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 {gamma}{delta} 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 {gamma}{delta} T cell-deficient settings. We found that {gamma}{delta} T cells were increased in tumour-bearing lungs, with an altered phenotype. CD27- and CD27+ {gamma}{delta} T cells differed in their localisation and interactions including their tropism for macrophages. Overall, we propose a model where CD27+ {gamma}{delta} 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, {gamma}{delta} T cells remain enigmatic regarding their role in lung adenocarcinoma. Raffo-Iraolagoitia et al. report that a subset of {gamma}{delta} T cells impairs the differentiation of tumour-associated macrophages into airway macrophages, relevant for the outcome of lung adenocarcinoma. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=111 SRC="FIGDIR/small/557344v1_ufig1.gif" ALT="Figure 1"> View larger version (49K): org.highwire.dtl.DTLVardef@e679f7org.highwire.dtl.DTLVardef@15152dforg.highwire.dtl.DTLVardef@17eaa5org.highwire.dtl.DTLVardef@2e0e47_HPS_FORMAT_FIGEXP M_FIG C_FIG