Liv Eidsmo

Chronic inflammatory skin diseases occur in fixed patches of the skin, indicating local immunopathology in disequilibrium with circulating immune cells. Tissue-resident memory T (Trm) cells provide localized immunity in barriers but are also implicated in inflammatory, autoimmune and malignant  skin diseases. We have identified functional dichotomy in human CD8+ Trm cells according to CD49a-expression with clinical implications in vitiligo and psoriasis. Now we plan to modulate the population of local Trm cells through interaction with their in situ renewal. Developmental cues, disease driving properties and survival pathways for precursors to functionally distinct Trm cell subsets will be investigated.  These inflammatory skin diseases are debilitating and stigmatizing for patients and cause a high burden on the health-care system. Our long-termgoal is to normalise the local Trm cell population in sites of chronic tissue diseases by eradicating pathogenic Trm cell precursors with novel drug application. Our work opens up for novel topical treatments aimed at long-term remission through eradication of specific Trm cell subsets, whilst sustaining Trm cells that maintain immunologicalbarrier functions.

The skin's immune cells form an effective protection against infections and tumors, but can also cause blemishes such as psoriasis and vitiligo. The balance between immune activity and tumor growth seems to be a crucial factor in tumor spread in malignant melanoma, a common type of cancer that is worryingly increasing in Sweden. New drugs activate immune cells in close proximity to tumors. The treatment works on some, but not all, patients with spread melanoma in some patients. An acceptable side effect of these new drugs is that some patients develop vitiligo mechanisms. The balance between effective tumor control and overactivity and vitiligo is an excellent model for learning more about the functioning of the immune system and how to improve immunotherapies. My laboratory works with basic studies of the skin's immune system. In this project, we want to transfer knowledge from healthy and inflamed skin to cancer-infested tissue. We will analyze the set and function of T cells in healthy skin, but also in metastatic melanoma, draining lymph nodes, lymph and blood. Advanced Molecular Biological Methods to Follow Single Families of T Cells and Try to Activate These to Combat Tumors. The goal is to create a basic understanding of T cell behavior in healthy tissue, melanoma and vitiligo. We want to understand how the activity in T cells changes in patients with spread cancer and we hope this is useful in the work of developing the next generation of immunomodulatory drugs. We also want to understand how the surrounding tissue reacts when T cells are activated in tumor tissue. Finally, we want to build a strong translational research environment at Karolinska Institutet, where doctors and researchers gather around the newest drugs and the sharpest experimental methods to advance the clinic and research.