CRCL research identify immune cells at the root of certain cancers

Nearly one in three cancers develops as a result of chronic inflammation, the origin of which is still poorly understood. In a new study, published this August 27 in the journal Nature Immunology, our CRCL “TGF-beta and immune response” team has identified lymphocytes involved in inflammatory processes, which may be implicated in the generation of these cancers. This work opens up new therapeutic and preventive perspectives.

About 30% of cancers develop as a result of localized chronic inflammation. This is particularly true for colorectal, small intestine, liver and pancreas cancers. ©Adobe Stock

Around 30% of cancers develop as a result of localized chronic inflammation. This is particularly true of certain cancers of the colorectal, small intestine, liver and pancreas. However, many questions remain unanswered to better understand the development of these cancers. Are one or more immune cells at the origin of the inflammatory process leading to cancer? If so, which cells?

Answering these questions is one of the aims of Julien Marie, REsearch Director at Inserm, and his team, to better understand how the disease is initiated.

The researchers were particularly interested in a population of immune cells, the TH17 lymphocytes, which are already known to be involved in numerous inflammatory diseases, such as multiple sclerosis and Crohn’s disease.

Immune cells that cause cancer

The hypothesis was that TH17 lymphocytes do not constitute a homogeneous population, but can in fact be divided into several subgroups. Using so-called “single-cell RNA sequencing” approaches, the scientists demonstrated this heterogeneity of TH17 cells within the intestine.

“More specifically, in this study, we show for the first time that there are in fact eight TH17 lymphocyte subtypes with distinct roles. One of them has a tumorogenic role, meaning that when certain activation brakes are lifted, it will contribute to the development of cancers. When these TH17 cells come into contact with previously healthy intestinal cells, they become cancerous”, explains Julien Marie.

The scientists then showed that this tumorigenic population is increased in patients at high risk of cancer. Finally, they also identified that a protein, the cytokine TGF-β, is capable of inhibiting the formation of tumorigenic TH17s.

“This study may raise questions for clinicians about the long-term use of immunotherapies in cancer patients, a treatment aimed at stimulating lymphocytes,” emphasizes Julien Marie.

While these therapies have transformed oncology treatments, they are also known to cause chronic intestinal inflammation. It is therefore important to consider, for a given patient, the risks of immunotherapy being accompanied by the emergence of tumorogenic TH17 lymphocytes, which could ultimately lead to the development of another cancer. Furthermore, this study lays the foundations for the development of new cancer-prevention therapies by blocking the appearance of the TH17 subtype implicated by the scientists in this work.

An intestinal TH17 cell-derived subset initiating cancer
Olivier Fesneau, Valentin Thevin, Valérie Pinet, Chloe Goldsmith , Baptiste Vieille, Saïdi M’Homa Soudja, Rossano Lattanzio, Michael Hahne, Valérie Dardalhon, Hector Hernandez Vargas¹, Nicolas Benech, and Julien C. Marie

 Nature Immunology, août 2024