Researchers have discovered that γδ T cells play a key role in shaping the immune environment of lung adenocarcinoma. In mouse models, these cells were found to accumulate in tumor-bearing lungs, recruited from the bloodstream rather than multiplying on-site. Once in the tumor, they showed reduced activation and produced fewer anti-tumor molecules, while clustering near blood vessels and tumor regions.
Advanced imaging and single-cell RNA sequencing revealed that γδ T cells interact directly with alveolar macrophages, forming immunological “synapses” and signaling through pathways such as CCL5-CCR1. These interactions push macrophages toward a profibrotic, scar-forming state, creating a tumor environment that supports cancer growth.
When γδ T cells were removed in experiments, profibrotic macrophages decreased, remaining macrophages became more inflammatory, and tumor collagen was less dense and disorganized. The findings suggest that Vγ1+ γδ T cells act as a “switch” promoting fibrosis and tumor progression, pointing to a potential target for new immunotherapies in lung cancer.