LINE 2: CANCER IMMUNOTHERAPY

Coordinators of the scientific report: A. Venuti - V. Ferraresi

The “Cancer Immunotherapy” line includes the activity of translational pre-clinical and clinical research, aimed at: improving the knowledge of anticancer immunological mechanisms; immunoevasion processes including those mediated by the microenvironment; optimizing the generation of vaccines, engineered T cells and the use of new molecules and immunomodulating strategies. Research is also based on the characterization of tumor-specific antigens and the analysis of the molecular/immune profile (immunoprofiling) of the individual patient. Finally, this Line is designed to identify new combination approaches to optimize therapy and better manage associated toxicity. It is increasingly evident that all anti-neoplastic therapies require activation of the host immune system to be effective, as historically demonstrated for CT and RT. Cancer immunotherapy represents the fourth approach to cancer treatment, together with surgery, RT and CT/biological therapy. It is a therapy that instructs and/or reactivates the cells of the immune system so that they can recognize and eliminate cancer cells. Tumors alter the immunocompetence of the host, triggering phenomena of immune resistance, in particular the functions of tumor-specific T-cells. Since many immunological checkpoints are triggered by receptor and ligand interactions, effective immunotherapies based on blocking these interactions by antibodies have developed. The identification of predictive biomarkers of response to immunotherapy is a further fundamental information to direct the clinician towards a personalized treatment. The characterization of tumor antigens has made it possible to conceive therapeutic vaccines but the need to design more effective vaccination therapies remains. At the same time, the molecular study of TCR allowed to engineer T cells with anti-tumor activity to be reinfused in the patient, although of problematic clinical applicability. Therapies with checkpoint inhibitors are effective but the identification of predictive response biomarkers is critical to select the patients most likely to benefit by limiting side effects. Fundamental elements for the success of the line are the biobanks and the use of samples from subjects at risk of cancer due to genetic, dietary, behavioural, environmental and occupational causes, and the multidisciplinary approach that includes biomolecular, immunological, virological, epidemiological, nutritional, radiodiagnostic, clinical and surgical expertise.