Characterizing the epigenetic features of tumor-associated macrophages

Conclusive insight in the complex interactions between the hypoxic TME and TAMs will directly contribute to the identification of new targets to counteract the negative effects of immune-editing and resistance to therapy. This proposal stands out in its novel approach of identifying and studying in vivo “epigenomic signatures” of hypoxic TAMs and how these inflammatory cells are projected towards pro-tumoral functions. We aim to understand the epigenetic regulation of TAMs under hypoxia, standing on the rationale that all the enzymes involved in epigenetic modifications are oxygen- and/or redox potential-dependent. By assessing the metabolic machinery assisting epigenetic modifications in hypoxic TAMs, we hope to offer proof-of-druggability of some of these key enzymes with the ultimate goal to reprogram the immunosuppressive TAM into powerful soldiers battling against cancer.