Newly Found Fibroblasts Help Lung Cancer Hide From the Immune System

Columbia University researchers have identified a previously unknown population of fibroblasts that may help lung tumours hide from the immune system. The cells, which express a gene called CHL1 not normally found on fibroblasts in healthy lungs, recruit immune-suppressing regulatory T cells to the edge of the tumour, creating a protective environment. The findings, published in Nature Immunology, come as lung cancer remains the leading cause of cancer-related death in the United States.

Fibroblasts are ordinary cells commonly found around solid tumours, but research over the past five to ten years has increasingly shown that some support cancer rather than simply surrounding it — work that has focused mostly on pancreatic cancer, with little known about lung cancer. Lead investigator Olivia Ringham, a graduate student at Columbia's Vagelos College of Physicians and Surgeons, found the CHL1 fibroblasts while profiling fibroblasts from a mouse model of lung cancer using single-cell transcriptomics, a technique that measures gene activity in individual cells to expose hidden cell populations.

Working with colleagues at Columbia and the University of Toronto, Ringham and senior author Nicholas Arpaia traced the fibroblasts' recruitment of regulatory T cells to a signalling protein called CXCL9. These T cells normally prevent excessive inflammation in the lungs, but in lung cancer the same function shields tumours from immune attack. When the researchers blocked this signalling in mice, fewer regulatory T cells gathered around the tumour, letting the immune system attack it.

The researchers then found the same CHL1 fibroblasts in human lung cancers. Patients whose tumours contained more of these cells had weaker immune responses and lower progression-free survival, an analysis of tumour specimens and patient data from Columbia's tissue bank found. Arpaia said targeting the T cells these fibroblasts recruit, or the fibroblasts themselves, could offer new treatment strategies, since the cells do not appear in normal lungs. Researchers do not yet know where the cells originate.