Vγ1 γδ T cells steer airway macrophages toward a profibrotic response in an autochthonous lung cancer mouse model
Year: 2026
Type: article
Abstract: Protecting 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. Summary Guardians 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
Source: Science Advances
Authors: Ximena L. Raffo-Iraolagoitia, Amanda J. McFarlane, Sarah Laing, Ryan Corbyn, Lindsey W. G. Arnott, Frédéric Fercoq, Lynn McGarry, Judith Secklehner, Marco De Donatis, John B. G. Mackey, Bjorn Kruspig, Robert Wiesheu, Ya-Ching Hsieh, Robin Shaw, Kai Rakovic, John Le Quesne, Graeme Clark, Colin Nixon, Crispin Miller, Kristina Kirschner, Calum C. Bain, Daniel J. Murphy, Seth B. Coffelt, Leo M. Carlin
Language: English
Topic: Immune cells in cancer
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,500
Awards: G1027702206, G1744002506, How do senescent stromal cells subvert the treatment response in acute lymphoblastic leukaemia?, G2250849917, G244503085, G3456572857, Cancer - Using complex state-of-art mouse models of cancer to improve the understanding and treatment of human cancer, G4960573433, G562897380, G6374696397, G6863181770, ICF: Neutrophils and cellular senescence: A vicious circle promoting age-related disease., G7901622682, G8295485578, Investigating the role of TGFβ in the functional imprinting of pulmonary macrophages in health and disease, G956923307
OpenAlex ID: W7133525614