Antonio Sica Principal Investigator View More
Our group uses genomic and proteomic approaches to map the functional relationship between tumor growth and alterations of myeloid differentiation that sustain the pathological expansion of immunosuppressive myeloid populations (Tumor-Associated macrophages/TAM) and Myeloid-Derived Suppressor Cells/MDSC). Particular attention is paid to the identification of inflammatory and metabolic circuits that guide the pro-tumor reprogramming of TAM and MDSC and their relevance in the resistance to anticancer therapies.
Pathological expansion of suppressor myeloid cells
Immunologic stress, such as infection and cancer, modifies the magnitude and composition of the hematopoietic output, a feature of immune regulation defined as ‘‘emergency’’ hematopoiesis, to guarantee proper supply of immune cells to increased demand. In cancer, chronic inflammation mediates tumor development by promoting a constant influx of inflammatory cells that undergo towards a tumor-promoting reprogramming that creates micro- and macro-environments that support cancer growth. Phenotypic and functional characterization of these expanding myeloid populations in cancer are however still poorly understood, as well as their pathological relevance. We focus on cancer-related inflammatory circuits and metabolic pathways that promotes the pathological expansion and heterogeneity of suppressor myeloid populations in cancer, aiming at identifying novel therapeutic targets to reverse tumor immunosuppression and retrieve the clinical efficacy of immunotherapy.
Epigenetic alterations of myeloid cells in cancer
Cancer-driven granulo-monocytopoiesis stimulates pathological expansion of tumor-promoting myeloid populations, mostly tumor-associated macrophages (TAM) and myeloid-derived suppressor cells (MDSC). Accumulation TAM and MDSC, enables cancer immune evasion and causes a bottleneck for cancer immunotherapy. Epigenetic alterations in myeloid precursors play a central role in the pro-tumor diversion of these cells. We aim to unveil the causal association between the epigenetic landscape acquired by tumor-associated myeloid cells and tumor immunosuppression, in the perspective to provide new indicators for both responsiveness to therapy and optimization of personalized anticancer treatments.
Antonio Sica Publications
Selected Publications: 20-25 publications listed in details with all the contributing authors, title of the papers, journal, dates. Garassino MC, Torri V, Colombo MP, Sica A. Choosing the Best Chemotherapy Agent ...