Avoiding destruction by immune cells is a hallmark of cancer, yet how tumors ultimately evade NK cell control remains incompletely defined. We have a project based upon the previously unrecognized TGF-b-dependent differentiation of conventional NK (cNK) cells in settings of lymphopenia and tumors. Strikingly, a higher proportion of cNK cells and their capacity for relatively high IFN-g/TNF-a production favored host protection from tumor initiation and growth, whereas tumor-localized NK cells that had differentiated appeared exhausted and corresponded with tumor growth. These data highlight the unexpected plasticity of cNK cells under pathophysiological conditions and reveal a novel mechanism by which tumors escape innate immune responses. We now wish to understand the role of innate-like cells in tumors and we wish to identify in preclinical models using various new fusion proteins the cancer therapeutic potential of specifically inhibiting NK cell differentiation and TGF-b signaling in cNK cells.
The project will concern research work in a team in the areas of cellular and molecular immunology, cancer cell biology, and angiogenesis in both mouse and human tumors. Theoretical training in immunology is highly desirable. Technical skills in animal experimentation, flow cytometry and/or cellular immunology are preferable.