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CD4+ T cells in moles may have a role in melanoma Tx

Photo by: the National Cancer Institute, public domain via Wikimedia Commons

Researchers have found that common moles on the skin contain a quantity of CD4+ T cells that could in principle be activated as a treatment for melanoma as well as providing a degree of protection against its recurrence.

The findings were published in Science Advances (June 23, 2021; 7(26):eabg4498).

In a press release from Massachusetts General Hospital (MGH) in Boston, the investigators behind the research explain that common moles are immunogenic targets for the T cells, but those cells are held in check by another set of cells—regulatory T cells (Tregs).

“Our research found that moles. . . are infiltrated by T cells that are primed to destroy the mole,” said senior author Dr. Shadmehr (Shawn) Demehri “These killer immune cells could be activated by immune-based therapeutics to not only eradicate the mole and the melanoma, but also generate a larger pool of immune cells that could help protect the individual against future development and progression of the cancer.” Activating resident CD4+ T cells, he added, could be especially important for high-risk populations, including people with many atypical moles, or those with a family history or their own history of melanoma.

Dr. Demehri is a dermatologist and an investigator in the Center for Cancer Immunology and the Cutaneous Biology Research Center at MGH.

As part of an effort to understand the relationship between melanocytic nevi and melanoma, the research team transplanted benign moles from humans into immunodeficient mice. After transplantation, the moles were rejected and killed by the CD4+ T cells.

“In humans, the moles were not being rejected because they were held in check by other immune cells known as Tregs, or immunosuppressive regulatory T cells,” explained the study’s first author Erik Schiferle, in the release. Schiferle is an investigator in the Center for Cancer Immunology and the Cutaneous Biology Research Center.

“Once in mice, however, the Tregs were inactive because they lacked the signalling present in humans,” he said. “Without the suppressive effect of Tregs, the CD4+ T cells were free to become activated and eliminate the mole. This biological cause and effect suggested to us that if you could block the Tregs that already exist in human moles, you could reactivate the anti-melanocyte CD4+ T cells to eliminate the mole while cross-protecting the patient against the melanoma developing and/or reappearing.”

The authors say that the next step could be the development of a treatment to suppress the Tregs at the site of the mole. They note that research is underway in a number of labs on agents that could suppress Tregs to combat a variety of cancers.

“One potential therapeutic approach is a localized or topical agent that could be applied on the skin to eradicate the mole,” said Schiferle.

The study findings also highlight the role of CD4+ T cells, according to the release. The authors note that more attention has been given to CD8+ T cells as antitumor cells.

“We believe they are as important as CD8+ T cells, if not more so, in rejecting their target, which in this case is a mole that could potentially lead to melanoma,” said Dr. Demehri. “Our lab is also investigating the role of CD4+ T cells in breast cancer, lung cancer, and other carcinomas as science begins to appreciate these immune cells as active and versatile players in both cancer treatment and immunoprevention.”


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