Certain immune T cells called tissue-resident memory cells are formed locally in the skin and other tissue, and protect against infections that they have encountered before. Now, researchers at Karolinska Institute (KI) and the University of Copenhagen have identified how the killer cells that protect our skin are formed and demonstrated that high levels of memory killer cells in cancer tissue correlate with a better survival rate in people with melanoma.

The study is published in Immunity in an article titled, “Human skin-resident CD8+ T cells require RUNX2 and RUNX3 for induction of cytotoxicity and expression of the integrin CD49a.”

“The integrin CD49a marks highly cytotoxic epidermal-tissue-resident memory (TRM) cells, but their differentiation from circulating populations remains poorly defined,” wrote the researchers. “We demonstrate enrichment of RUNT family transcription-factor-binding motifs in human epidermal CD8+CD103+CD49a+ TRM cells, paralleled by high RUNX2 and RUNX3 protein expression.”

“We don’t know so much about how and why memory killer cells are formed in the skin and what it means for cancer patients,” said Yenan Bryceson, PhD, professor at the department of medicine, Karolinska Institute. “Finding out how these cells develop enables us to contribute to the development of more efficacious immunotherapy for diseases like melanoma.”

The study charted the development of memory killer cells in human skin, performed as a collaborative effort between KI researchers Beatrice Zitti and Elena Hoffer. The researchers isolated T cells from the skin and blood of healthy volunteers and used advanced techniques to examine gene activity and expression of different proteins.

After knocking out specific genes, they also demonstrated which genes are required for the maturation of memory killer cells in tissue. They went on to study tumor samples from melanoma patients and found that those with a higher rate of survival also had a larger accumulation of epidermal memory killer cells.

“We’ve been able to identify several factors that control the formation of memory killer cells, which play an important part in maintaining healthy skin,” said Liv Eidsmo, PhD, dermatologist and professor at the University of Copenhagen in Denmark and researcher at KI. “There’s a fine balance between effective protection against tumors and infections in the skin and contribution to inflammatory diseases like vitiligo and psoriasis.”

The researchers hope to use their findings to optimize the immunotherapy-induced T-cell response to improve its ability at eliminating cancer cells in tissues.

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