Prof. Yardena Samuels

Our overarching goal is to provide an unprecedented, thorough, multifaceted understanding of interactions of melanoma cells with the immune system. Specifically determining mechanisms underlying aberrant peptide production, peptide-MHC presentation, and T-cell recognition in melanoma. We do this by systematic interrogation of the cancer immunopeptidome to identify novel canonical and non-canonical cancer antigens and quantify their presentation. We then comprehensively assess the functional qualities of actionable antigens by quantitatively charting the immunopeptidome in-vivo, to delineate how these neoantigen qualities impact the immune response. We also establish controlled in-vivo models to tease apart various neoantigen qualities for the establishment of rational cancer vaccine modalities. For these aims, we use pioneering tools and advanced mapping of the cancer peptidome in melanoma, which has already revealed novel antigenic sources. Our research approach combines comprehensive quantitative immunopeptidomics, novel imaging and computational approaches, advanced functional assays and novel mouse models. Our projects provide a fresh view of melanoma-immune interactions, new research tools and pipelines, cancer-specific antigen targets for immunotherapy and, more broadly, a paradigm for addressing similarly complex questions in other cancers.