Vγ1 γδ T cells steer airway macrophages toward a profibrotic response in an autochthonous lung cancer mouse model.

Summary

In an autochthonous lung cancer mouse model, tumors expand specific γδ T cell subsets, with Vγ1 γδ T cells directing airway macrophages toward a profibrotic state. This reveals a γδ T cell–macrophage axis that can promote tumor-associated fibrosis and reshape the tumor microenvironment.

Key Findings

• Tumors in a genetically engineered mouse model expand γδ T cell subsets, including Vγ1 cells.
• Vγ1 γδ T cells skew airway macrophages toward a profibrotic phenotype within the tumor microenvironment.
• Findings define a γδ T cell–macrophage axis linking tumor growth to fibrotic remodeling.

Clinical Implications

Targeting Vγ1 γδ T cell–macrophage crosstalk or downstream profibrotic programs may mitigate tumor-associated fibrosis and improve response to therapy in lung cancer.

Limitations

• Preclinical murine findings require validation in human tissues and across tumor subtypes.
• Therapeutic modulation of the identified axis was not tested in interventional studies.

Future Directions

Validate γδ T cell–macrophage pathways in human lung cancer, define molecular mediators of profibrotic programming, and test targeted interventions to disrupt this axis.