Experimental oncology
Immuno-biotherapy of melanoma and solid tumors
Our research focuses on the mechanisms of tumor immune evasion (Sterol-based tumor immune evasion mechanisms) and on the characterization and development of immune niches promoting and sustaining antigen-specific T cells endowed with optimal antitumor functions (Characterization of immune niches fueling antitumor T cells). Finally, by high dimensional flow cytometry analysis of melanoma patients’ samples, we are interested to evaluate the features of immune subsets correlating with clinical outcomes (Analysis of immune cells landscape in melanoma patients).
Research activity
Sterol-based tumor immune evasion mechanisms. We have investigated and dissected the role played by Liver X Receptor/(LXR) ligands in dampening the antitumor immune response. LXRs blunt inflammatory responses by regulating the reverse cholesterol transport pathway. In the tumor microenvironment (TME), LXRs and their ligands promote tumor growth by inhibiting dendritic cell migration to draining lymph nodes and by recruiting neutrophils endowed with pro-angiogenic and immune suppressive abilities. In collaboration with the University of Perugia, we have developed several LXR antagonists to investigate how they modulate immune cells behavior in pre-clinical tumor models in vivo, as well as in vitro. These studies will shed lights on the potential therapeutic activity of these compounds, the related mechanism(s) of action and will allow to improve immunotherapy strategies by reprogramming cholesterol metabolism of immune cells.
Characterization of immune niches fueling antitumor T cells. High dimensional flow cytometry and single cell transcriptomics studies have highlighted key features of tumor-infiltrating immune cells associated with optimal antitumor responses following immunotherapy. In mouse and human tumors, the generation of tumor-specific T cells endowed with stem cell memory features, are associated with prolonged overall survival of tumor-bearing mice and humans. We are currently investigating the spatial cellular and molecular regulation of the interactions among various subsets of immune cells in lymphoid organs, capable of promoting and sustaining the generation and maintenance of antitumor T cells endowed with optimal antitumor abilities. The identification and molecular characterization of these interactions will allow to develop more effective antitumor strategies in cancer patients and methods to generate more fit antitumor T cells for adoptive cell therapy studies.
Analysis of immune cells landscape in melanoma patients. High dimensional flow cytometry analysis of tumor and blood samples of melanoma patients undergoing immunotherapy. This analysis aims to identify and characterize immune cell subsets differentially expressed by responding and non-responding patients.
