Chronic Inflammation May Drive Colon Cancer

Chronic Inflammation May Drive Colon Cancer

shutterstock_130094669In a recent study entitled “Immature myeloid cells directly contribute to skin tumor development by recruiting IL-17–producing CD4+ T cells,” a research team identified that a specific type of immune cell, immature myeloid cells, are the first step towards the development of chronic inflammation-associated tumors, such as colon cancer. The study was published in the Journal of Experimental Medicine.

Inflammation is a protective immunovascular response that is activated upon harmful stimuli, such as pathogens, toxic compounds or even damaged tissues. However, while inflammation is a crucial response of the body’s defense, chronic inflammation, i.e., a persistent, unresolved inflammation, is known to contribute to cancer development such as colon cancer, basal cell carcinoma, lung, liver, among others. However, as inflammation is a complex process, the role of specific cells, mainly myeloid cells, linking inflammation to cancer remains largely unknown.

Here, a research team led by Dmitry Gabrilovich, M.D., Ph.D., at The Wistar Institute in Philadelphia discovered that a specific type of myeloid cells, granulocytic immature myeloid cells (IMCs), accumulate in inflammatory conditions that lead to the development of tumors, as those in the skin and colon.

To understand the role of these cells in tumor development, the authors developed a transgenic mouse that accumulates these cells in the skin but without inflammation. They found that upon exposure to a tumor-inducing agent, TPA (short for 12-O-tetradecanoylphorbol-13-acetate), these mice had a significant increase in the burden of benign tumors (so called papillomas), an established step towards skin cancer. The team performed further studies and discovered that IMC’s role in cancer was not mediated by the inhibition of an immune response, but rather by inducing the recruitment of a specific type of T cells: CD4+ T cells. These cells ultimately induce an abnormal proliferation of skin cells, keratinocytes, leading to skin cancer.

Furthermore, researchers identified that the molecular switches governing this process includes the CCL4 chemokine, released by granulocytic IMCs cells and responsible for the attraction of T cells, which in turn produce a proinflammatory cytokine, interleukin-17 (IL-17), a player already established as playing a role in tumor development.

Vinit Kumar, Ph.D., one of the study co-authors and member of Gabrilovich laboratory noted in a press release, “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.”

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