Our skin comprises specialized long-lived killer cells that protect against intruders. Researchers at Karolinska Institutet in Sweden and the University of Copenhagen in Denmark have now identified how these cells are formed, and shown that top levels of memory killer cells in cancer tissue correlate with a greater survival rate in individuals with melanoma. The study is published within the journal Immunity.
Certain immune T cells called tissue-resident memory cells are formed locally within the skin and other tissue, and protect against infections that they’ve encountered before. A few of them express proteins that enable them to kill infected cells. These “memory killer cells” may contribute to the inflammatory skin disorders vitiligo and psoriasis. Recent research has shown that also they are involved within the body’s immune response to numerous cancers.
Various responses to treatment
The memory killer cells have been shown to answer immunotherapy, a Nobel Prize-winning cancer therapy involving the tweaking/activation of the immune system. Immunotherapy is often administered as a complement to other cancer treatments, and there may be considerable variation in how patients reply to it.
We do not know a lot about how and why memory killer cells are formed within the skin and what it means for cancer patients. Checking out how these cells develop enables us to contribute to the event of more efficacious immunotherapy for diseases like melanoma.”
Professor Yenan Bryceson, Department of Medicine (Huddinge), Karolinska Institutet
The study charted the event 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 look at gene activity and expression of various proteins. This allowed them to discover T cells within the blood with the potential to turn into memory killer cells in skin or other tissues. After knocking out specific genes, they might also show which genes are required for the maturation of memory-killer cells in tissue.
More practical immunotherapy
The researchers then went on to check tumor samples from melanoma patients and located that those with a better rate of survival also had a bigger accumulation of epidermal memory killer cells.
“We have been capable of discover several aspects that control the formation of memory killer cells, which play a vital part in maintaining a healthy skin,” says Liv Eidsmo, dermatologist and professor on the University of Copenhagen in Denmark and researcher at Karolinska Institutet in Sweden, who led the study with Professor Bryceson. “There is a high quality balance between effective protection against tumors and infections within the skin and contribution to inflammatory diseases like vitiligo and psoriasis.”
The researchers now aim to harness their findings to optimize the immunotherapy-induced T-cell response to make it even higher at eliminating cancer cells in tissues.
The study was conducted in collaboration with the Karolinska University Hospital, Nordiska Kliniken and Vrinnevi Hospital. It was financed by grants from Novartis, the EU (Marie Skłodowska-Curie Actions), KI Foundations and Funds, the Swedish Research Council, the Ragnar Söderberg Foundation, the Swedish Medical Society, Region Stockholm (ALF scheme), the Swedish Psoriasis Foundation, the Swedish Dermatology Foundation, the Swedish Cancer Society, the Göran Gustafsson Foundation, Stockholm City Council, the Karolinska Institutet Centre for Progressive Medicine (CIMED) and the Knut and Alice Wallenberg Foundation.
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Journal reference:
Zitti, B., et al. (2023) Human skin-resident CD8+ T cells require RUNX2 and RUNX3 for induction of cytotoxicity and expression of the integrin CD49a. Immunity. doi.org/10.1016/j.immuni.2023.05.003.