Immunophenotyping Core A central unifying hypothesis of this research program is that MCC ? both viral and UV-damage associated - is a highly immunogenic tumor and, consequently, amenable to immune-oncologic intervention. This hypothesis is supported by the presence of virus-specific T cells and antibodies in many of the patients as well as an approximate 50% ORR in metastatic MCC patients treated with monotherapy anti-PD-1 or anti-PD-L1 monoclonal antibodies (mAbs). Unfortunately, many patients still fail to respond to PD-1 blockade. The overarching goal of the Immunophenotyping Core is to provide cutting-edge, slide-based technologies to interrogate the tumor microenvironment, in particular, to apply multiparametric immunohistochemistry (mIHC) to understanding the critical cell-cell interactions occurring within the tumor microenvironment (TME) that either enable or disable productive anti-tumor immune responses. We anticipate that these mechanistic insights will inform future combination immune-oncology trials in MCC patients.
Immunophenotyping Core The Immunophenotyping (IP) Core will support all three projects by providing cutting-edge, slide-based technologies and immunopathology expertise to understand the interaction between tumor cells, stromal cells and immune cells within the tumor microenvironment (TME). Although Merkel cell carcinoma (MCC) is a highly immunogenic tumor, many patients fail to respond to current immunotherapy with anti-PD1 agents. We hypothesize that through analyzing and understanding the cell-cell interactions (i.e. the social network) of the TME, we will learn what controls the generation of productive versus abortive anti-tumor immune responses, and be able to apply that understanding to improve future therapy.
