Hanna Eriksson

Immune checkpoint inhibitors and targeted therapies have improved the outcome for metastatic cutaneous melanoma (CM) patients. The histopathological and molecular characterization of metastatic CM and the understanding of the microenvironment are thus critical for more effective patient management and to design biologically driven clinical trials. The overall purpose is to improve CM survival through by identifying and ultimately validating clinically impactful biomarkers and novel therapeutic targets to optimally inform clinical decision-making. Our approach consists of multi-omics-based unsupervised and clinical- outcome- and pathological-outcome-based stratified analyses including machine learning of matched and curated tissue and plasma biospecimens from CM. This will expand the concept of liquid biopsies to include not only DNA sequences, but also proteins sequences and opens up for the possibility to study fundamental biological processes also in brain metastatic disease. The impact of hyperinflammation on therapy responses will be investigated in in vitro/in vivo models. This will give an unique insight of the interplay between the immune system, the individual tumors and metastatic niches. In addition, patient related outcome measures will be analyzed in parallell. We predict that these findnings will provide a rationale for a combinatorial immune therapy within a clinical trial. In future this will improve and further advance  presicion medicine in advanced CM.

The incidence of melanoma is increasing in Sweden. Survival rates differ between different stages of the disease and early detection is important. Patients with brain metastases have a very short survival. The treatment results in disseminated melanoma have been significantly improved by immune receptor blocking treatments, which provide an increased immune response directed against the tumor but which can cause severe side effects. A percentage of patients achieve long-term survival with the immunotherapy. Markers that predict therapy response and side effects are lacking. There is a great need to improve the management and treatment of melanoma at all stages of the disease. The objective is to analyze clinical and biological markers that can benefit the patient with a focus on high-risk/advanced melanoma. We want to improve diagnostics and early detection of melanoma as well as follow treatment response and side effects. The project will develop new methods such as artificial intelligence for diagnostics, analyze large register data and examine blood and tumor samples during treatment. In the blood, we want to examine proteins and small transport vesicles (so-called exosomes) that the cells leave behind. By developing the spatial technologies, gene expression at the cellular level can be analyzed in tumor tissue and visualized. The project is a unique opportunity to find new risk groups and individuals with a worse prognosis in the disease as well as treatment predictive markers by using new technology and clinical samples in collaboration with other research groups. The project will specifically provide increased knowledge about the disease, with a focus on brain metastases, about treatment side effects and how the disease differs between men and women during treatment. Our project will thus contribute to improving the care and treatment of melanoma through all stages of the disease. In the future, we hope to be able to develop new treatment strategies within the framework of clinical trials.