In a remarkable breakthrough, scientists from Karolinska Institutet and the University of Copenhagen have unraveled the mysteries surrounding the formation of specialized long-lived killer cells in our skin. These extraordinary cells have been found to provide a shield against intruders, and an astonishing correlation has been identified: higher levels of memory killer cells in cancer tissue correspond to a better survival rate among individuals with melanoma. The groundbreaking study, shedding light on this vital defense mechanism, has been published in the prestigious journal Immunity.
These exceptional immune T cells, known as tissue-resident memory cells, are generated locally within the skin and other tissues, effectively safeguarding against recurring infections. A subset of these cells expresses proteins that equip them with the ability to eliminate infected cells, earning them the name “memory killer cells.” Intriguingly, these very cells also contribute to inflammatory skin disorders such as vitiligo and psoriasis. Recent research has uncovered their involvement in the immune response against various types of cancer as well.
Notably, memory killer cells have displayed responsiveness to immunotherapy, the Nobel Prize-winning cancer treatment that harnesses the power of the immune system. However, patient responses to immunotherapy vary significantly, and much remains unknown about the formation of memory killer cells in the skin and its implications for cancer patients. Professor Yenan Bryceson from the Department of Medicine (Huddinge) at Karolinska Institutet emphasizes the significance of understanding the development of these cells, as it paves the way for more effective immunotherapy options, particularly for diseases like melanoma.
To investigate the formation of memory killer cells in human skin, the study involved collaborative efforts between researchers Beatrice Zitti and Elena Hoffer from Karolinska Institutet. T cells were isolated from the skin and blood of healthy volunteers, and sophisticated techniques were employed to examine gene activity and the expression of different proteins. This meticulous analysis allowed the identification of T cells in the blood that possess the potential to mature into memory killer cells within the skin or other tissues. By selectively knocking out specific genes, the researchers also unveiled the genes essential for the maturation of memory killer cells in tissue.
Taking their investigation a step further, the scientists examined tumor samples from melanoma patients and made an intriguing discovery. Patients with a higher survival rate displayed a substantial accumulation of epidermal memory killer cells. Liv Eidsmo, a dermatologist and professor at the University of Copenhagen and a researcher at Karolinska Institutet, who co-led the study with Professor Bryceson, highlights the delicate balance between providing effective protection against tumors and infections in the skin while potentially contributing to inflammatory diseases like vitiligo and psoriasis.
With their groundbreaking findings, the researchers aim to optimize the T-cell response induced by immunotherapy, utilizing their newfound knowledge to enhance the eradication of cancer cells within tissues. The study was conducted in collaboration with the Karolinska University Hospital, Nordiska Kliniken, and Vrinnevi Hospital, and received financial support from esteemed organizations such as Novartis, the EU (Marie Skłodowska-Curie Actions), and numerous foundations and councils devoted to advancing medical research and patient care.