A recent study led by researchers at The Wistar Institute revealed for the first time the cellular mechanism underlying cancer development induced by chronic inflammatory diseases. The study, entitled “Immature myeloid cells directly contribute to skin tumor development by recruiting IL-17–producing CD4+ T cells,” was published in the Journal of Experimental Medicine.
Inflammation is known to be an essential and natural mechanism by which the body recovers from injury and disease. Chronic inflammation, however, has been directly linked with different types of cancer, although the reasons underlying this association at the cellular level are not clear.
“While we know that cancer is initiated because of genetic alterations, we also know that cancer’s development relies heavily on environmental factors,” said the study’s senior author Dr. Dmitry Gabrilovich in a news release. “Inflammatory conditions are closely linked to cancer, yet it’s a very complex process, making it difficult to determine how certain components contribute to the development of cancer.”
Researchers have now identified a complex mechanism underlying the development of these types of cancer. They found that inflammatory conditions are linked to specific myeloid cells named immature granulocytic cells. With the aid of transgenic mice, the team generated conditions which allowed the accumulation of granulocytic cells in the skin in the absence of typical inflammation methods like infection or tissue damage. The mice were then exposed to a tumor-promoting substance named TPA, which resulted in a significant increase in the generation of benign tumors (papillomas), normally one of the first signs of skin cancer.
The team found that granulocytic cells appear in the skin and induce the migration of lymphocytes (a type of white blood cell) by releasing a specific molecule called chemokine CCL4. Lymphocytes subsequently induce the atypical growth of keratinocytes (the predominant skin cell type in the epidermis). CCL4 recruits CD4+ T cells (helper cells that play an important role in the immune system) that produce a proinflammatory cytokine called interleukin-17 (IL-17), which has already been associated with chronic inflammation and inflammatory cancers.
Researchers suggest that by a multi-step mechanism, granulocytic cells accumulate and induce tumor formation, followed by CD4+ T cells’ recruitment and subsequent production of IL-17, which all together results in the development of inflammatory cancers. “If we are able to target these granulocytic cells directly, we may be able to prevent the inflammatory effects of IL-17, which would provide a great benefit to individuals with a high risk of developing these types of cancer,” said one of the study’s co-authors Dr. Vinit Kumar.
Although the study has been conducted on skin cancer, the research team believes that the findings can be applied to any type of cancer that is associated with chronic inflammation. They suggest that the newly discovered cellular mechanism can offer a new range of potential therapeutic targets to halt the generation and growth of tumor cells in patients at risk of developing inflammation-related cancers.