In mice, fibroblasts in lung tumors recruit immune-suppressing cells

Olivia Ringham spent hours studying images of cells gathered around lung tumors. At Columbia University, that painstaking work helped reveal a previously unknown population of fibroblasts—support cells often found around solid tumors—that appears to help lung cancer evade immune attack. The cells were identified in a mouse model using single-cell transcriptomic profiling, a method that reads gene activity one cell at a time.

The fibroblasts carry CHL1, a gene not normally found on fibroblasts in healthy lungs. Ringham and senior author Nicholas Arpaia found that the cells produce CXCL9, a signaling protein that recruits regulatory T cells to the tumor border. Regulatory T cells normally keep the lung’s immune system from overreacting to material brought in with every breath. In lung cancer, the same restraint can shield the tumor.

The team, working with colleagues at Columbia and the University of Toronto, blocked the signaling system in mice by inactivating the relevant genes. That reduced the buildup of regulatory T cells and permitted an immune response against the tumor. In human lung-cancer specimens, tumors containing more CHL1 fibroblasts showed weaker immune responses and lower progression-free survival, according to the researchers’ analysis of Columbia’s tissue bank and patient data.

So what changes, concretely? The study gives researchers a potential target that is absent from normal lungs: the CHL1 fibroblasts themselves. Blocking the CXCL9 signal, targeting the regulatory T cells they attract, or preventing the fibroblasts’ transformation could eventually help expose tumors to the immune system. None of those approaches is yet an established treatment.

The evidence is still preclinical. The mechanism was tested in mice, while the human data show a relationship between CHL1 fibroblasts, immune suppression, and progression-free survival rather than proving cause and effect. For a disease that remains the leading cause of cancer-related death in the United States, the advance is a more precise map of how some lung tumors protect themselves—not a therapy ready for patients.