MelImmuneOrg SIGNED

Project "MelImmuneOrg" data sheet

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 Project objective

Cancer progression is a complex process that depends on the interplay between tumor cells, tumor microenvironment, and the immune system. Inhibiting immunosuppression is beneficial for cancer patients. Although these therapies are promising they are successful only in part of the patients. Tumors are composed of distinct cell types with different phenotypes, that influence the efficacy of immunotherapies. Therefore, in order to better understand tumor biology and response to treatment, it is necessary to profile protein expression while preserving spatial information. Multiplexed Ion Beam Imaging by Time of Flight (MIBI-TOF) is a method in which antibodies conjugated to metals are used to simultaneously visualize dozens of proteins in intact tissue specimens by secondary ion mass spectrometry. Here we suggest to uncover the immune profile and organization within the tumors of melanoma patients undergoing immunotherapy using MIBI-TOF. My first objective is to characterize the tumor-immune microenvironments to understand how these are structured across patients and discover predictive features of response to immunotherapies. My second objective is to analyze the intratumor heterogeneity (ITH) of melanoma patients by exome sequencing. I will examine whether there are genetic correlates between ITH, immune microenvironment and response to therapy. Finally, my third objective will be the manipulation of individual hits to test their functional significance in tumor-immune architecture in murine models. By joining Dr. Keren’s lab that masters the MIBI-TOF technology, I will acquire this state-of-the art technique, as well as develop lab management and organization skills, and I will meet leader scientists from the immune-oncology field. This proposal will promote my competitiveness to gain an independent researcher position.