Nearly 30% of cancers appear as a result of chronic local inflammation. This is the case for certain colorectal, small intestine, liver and pancreatic cancers. As a reminder, inflammation is the immune system’s reaction to an external or internal attack on the body. When it persists, this reaction can end up damaging nearby cells and causing cancer. This mechanism is known, but scientists had not previously identified the immune cells involved, nor whether it was one or several cells at work.
French researchers from the Lyon Cancer Research Center (Inserm/CNRS/Claude-Bernard Lyon 1 University/Léon Bérard Center) chose to focus on TH17 lymphocytes, immune cells known to be involved in chronic inflammatory bowel diseases such as Crohn’s disease. The scientists’ intuition was that this family of cells constituted a heterogeneous population, with a specific role assigned to each group. They targeted their research, in mice, on TH17 cells in the intestine by performing “single-cell RNA sequencing”, a recent technique that allows the genetic program of each cell to be studied individually.
Towards new therapeutic approaches?
Result: “in this study, we show for the first time that there are in fact eight subtypes of TH17 lymphocytes with distinct roles. One of them has a tumorigenic role, that is to say that when certain activation brakes are lifted, it will contribute to the development of cancers. When in contact with these TH17 cells, the cells of the intestine that were healthy until then will become cancerous”, explains Julien Marie, research director at Inserm, quoted in a press release from the institute.
While immunotherapy, which has revolutionized cancer treatment, consists of stimulating immune cells to fight tumors, could it also stimulate TH17 cells involved in the onset of cancer? “This study can question clinicians about the use, over a long period, of immunotherapies in patients with cancer, a treatment that aims to stimulate lymphocytes,” emphasizes Julien Marie.
This work, published in the journal Nature Immunology in July, also revealed that this subgroup of tumorigenic cells is present in greater numbers in people at high risk of cancer. This could pave the way for early diagnosis and better prevention in people at risk.
Another discovery is that of a protein capable of inhibiting the formation of tumorigenic TH17 lymphocytes. A discovery that lays the foundations for the development of new preventive therapies against the formation of the incriminated TH17 subtype.
Note: while several cancers are linked to chronic local inflammation, this study only focuses on intestinal cancer.
