LINE 2: CANCER IMMUNOLOGY AND IMMUNOTHERAPY
The role of the immune system in controlling cancer growth and eventual progression is a paradigm within the field of oncoimmunology. Numerous studies have shown that all anti-cancer therapies require stimulating the host immune system in order to be effective, and where immunotherapy treatments in clinical practice constitute a new frontier in oncology. Despite the results obtained in numerous malignancies, the mechanisms of innate and acquired resistance which limit clinical efficacy to a percentage of patients still remains to be elucidated. The "Cancer Immunotherapy" line of research encompasses pre-clinical and clinical projects aimed at identifying pro- and anti-tumor immunological mechanisms mediated by the microenvironment and are involved in resistance to immunotherapy treatments such as the immune checkpoint inhibitor (ICI) therapy and engineered T cells (CAR-T), in order to identify selection criteria for patient stratification and novel immune-related pathways as therapeutic targets. Besides studies regarding the tumor microenvironment (TME) and assessing the role of biomechanical signals on cells of the immune system, researches are also pursuing another avenue involving the analysis of the immunoprofiling, also using new DNA and RNA sequencing technologies up to single-cell resolution, since streams of big data obtained via omics technologies serve to create mathematical models for designing personalized immunotherapy treatments. Along with immunomodulatory therapies, effective vaccine therapies and the identification of neo-antigens as possible targets are ever more remaining critically relevant. Combinations of ICI with vaccine therapies both in the early lines and in the immune resistance setting represent an important and innovative field of research. Moreover, in order to define new combination therapies that include radiotherapy or other loco-regional treatments also comprising oncolytic viruses, it is critical to identify the changes in the immune system dynamics during loco-regional treatment under different types of treatment or different doses of radiation fractionation. Key elements in achieving the goals of this line are biobanking tissue specimens and biological fluids, digital pathology analyses, and novel viable tissue macro-sections and 3D models, integrated with radiological and clinical information from patients, employing a multidisciplinary approach that includes expertise from across various disciplines involving radiologists, surgeons, pathologists, oncologists, radiation oncologists, immunologists, virologists, and molecular and computational biologists.
The main objectives of the research line include: (a) identifying TME-mediated pro- and anti-tumor immunological mechanisms involved in resistance to immunotherapy treatments; (b) detecting clinico-biological factors predictive of immunotherapy response and biomechanical signals in modulation of immune response; (c) analyzing immunoprofiling and identifying biomarkers derived from high-throughput assays; (d) providing a definition of combinations of ICI with vaccine therapies, gene therapy, and radiotherapy; (e) outlining the role of viral infections in cancer; (f) identifying therapeutic targets for reactivation of immune response in cancer
Indicators: Communicate/participate in national and/or international conferences, organization of specific intra/extramoenia seminars/conferences. Identifying patentable results. Submit applications for and obtaining competitive Grants.