Immunotherapy revolutionized cancer treatment, leading to durable responses even in the most aggressive cancer types, such as melanoma. Despite this success, more than 50% of melanoma patients do not respond to treatment. Our previous work showed an association between the metabolic state of the melanoma cells with immunotherapy response. In the current project we aim to increase treatment efficacy by combining immunotherapy with metabolic drugs in-vitro, in-vivo and in patients. We will then examine the effects on all cell populations in the tumor microenvironment including the melanoma cancer cells and immune cells. Through development of single cell proteomics approaches and integration with single cell RNA-sequencing, we aim to obtain a comprehensive functional view of melanoma response (Figure 1). Our collaborative work involves analysis of patient samples obtained from the Sheba Medical Center, epidemiological analysis of large international clinical databases, and experimental research at Tel Aviv University and at the Sheba Medical Center. In the first stages of the project we already obtained melanoma patient samples from the Sheba Medical Center, pre- and post-treatment with immunotherapy, and characterized 12 cell populations from mouse tumors as the basis for the study of their changes upon treatment (Figure 2). Our automated proteomic workflow enabled identification of thousands of proteins including the key markers of each population. These experiments highlight the great potential of our research to promote the technology towards deep understanding of treatment responses.
The research is performed in collaboration with the Sheba Medical Center.