Newly identified cells protect lung tumors from immune attacks
· News-MedicalThe new cells were discovered as part of a wider project to understand the roles of fibroblasts-seemingly normal cells often found around solid tumors. "In the past five or ten years, a lot of research has shown these fibroblasts are helping the cancer and their activity is linked to patient outcomes," says Olivia Ringham, a graduate student at Columbia's Vagelos College of Physicians and Surgeons and lead investigator on the project.
"Much of the earlier work on these cancer-associated fibroblasts has focused on pancreatic cancer, but little is known about the cells in lung cancer," says Nicholas Arpaia, associate professor of microbiology and immunology, senior author of the study, and Ringham's adviser.
Cell-by-cell analysis
Ringham found the new cells while examining all fibroblasts from a mouse model of lung cancer with a technique called single-cell transcriptomic profiling. "Single-cell transcriptomics has really had a huge development on the field over the last decade," says Ringham. "It's a great way to find hidden cell types and understand what those cells do."
Ringham and Arpaia eventually learned that the newly identified fibroblasts promote lung cancer by recruiting a population of regulatory T cells to the border of the tumor. Regulatory T cells usually protect the lung by keeping the immune system in check. "There are all these different environmental antigens that come into your lung at any given moment," says Ringham. Without regulatory T cells to keep the system balanced, every breath would trigger a strong inflammatory response.
But in the setting of lung cancer, the immunosuppression created by the regulatory T cells only serves to protect the tumor.
Human lung cancer
The same fibroblasts also exist in human lung cancers, where they appear to recruit regulatory T cells and impact patient outcomes. Using tumor specimens and patient data from Columbia's extensive tissue bank, Ringham found that patients whose tumors had more CHL1 fibroblasts also had reduced immune responses against their cancers and lower progression-free survival rates.
Targeting the regulatory T cells drawn in by the fibroblasts could unleash the immune system and be a promising strategy against lung cancer, Arpaia says.
Because they don't appear in normal lungs, the new CHL1 fibroblasts may also be a potential target. "Where do these cells come from? How are they formed?" asks Ringham. "If we could stop that transformation, it could provide a great benefit."
Source:
Columbia University Irving Medical Center
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