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

## TL;DR

This study shows that a specific type of T cell, Vγ1 γδ T cells, influences airway macrophages to become profibrotic in a mouse model of lung cancer.

## Contribution

The study identifies Vγ1 γδ T cells as key drivers of profibrotic macrophage responses in lung cancer.

## Key findings

- Tumors expand both CD27+ and CD27− γδ T cells, with CD27− cells enriched in tumors.
- Vγ1 γδ T cells are linked to profibrotic airway macrophages in lung cancer.
- Depletion of Vγ1 γδ T cells reduces profibrotic macrophages in tumor-bearing mice.

## Abstract

γδ T cells are important for host defense at the respiratory mucosa, acting directly or through interactions with other cells. However, how γδ T cells influence other immune cells in the lung remains unclear. Using a genetically engineered mouse model of lung cancer, we show that tumors drive expansion of both CD27+ and CD27− γδ T cells. Advanced microscopy techniques indicated that CD27− γδ T cells are enriched in tumors, whereas CD27+ γδ T cells are more prone to interact with macrophages in tumor-associated adventitial cuffs. SiglecFlow profibrotic airway macrophages were more prevalent in lung tumor-bearing mice than tumor-free mice. This profibrotic subset was reduced in lungs when the cancer model was crossed to Tcrd knockout mice or treated with Vγ1-depleting antibodies but not in TcrgV4/6 knockout mice. Thus, our findings implicate Vγ1 γδ T cells in driving tumor-associated airway macrophage functional imprinting. Determining the translatability to human health may offer new avenues for refining patient management and immunotherapeutic strategies.

In lung cancer, airway macrophages are modulated by an unconventional T cell subset, relevant to care for pulmonary comorbidities.