Scientific Leads:
Nisticò Paola, Toietta Gabriele, Minuti Gabriele, Paolini Francesca

Description

The role of the immune system in controlling neoplastic growth and progression is a central paradigm in tumour immunology. Numerous studies have shown that effective anticancer therapies require activation of the host immune system, and that the clinical implementation of immunotherapeutic treatments represents a major frontier in oncology. Despite the results achieved across several tumour types, the innate and acquired resistance mechanisms that limit clinical efficacy to a subset of patients remain to be fully elucidated. The “Cancer Immunotherapy” research line includes preclinical and clinical projects aimed at identifying pro- and antitumour immune mechanisms mediated by the tumour microenvironment and involved in resistance to immunotherapeutic treatments, such as immune checkpoint inhibitors (ICIs) and engineered T cells (CAR-T cells). The ultimate aim is to identify selection criteria for patient stratification and novel immune-related pathways as therapeutic targets. In parallel with studies of the tumour microenvironment (TME) and analyses of the role of biomechanical signals in immune cells, research activities will also focus on patient immunoprofiling, including the use of emerging DNA and RNA sequencing technologies down to single-cell resolution. The big-data streams generated through omics technologies will support the development of mathematical models for the design of personalised immunotherapeutic strategies. Among immunomodulatory treatments, increasingly effective vaccination strategies and the identification of neoantigens as potential targets remain highly relevant. The combination of ICIs with cancer vaccines, both in earlier treatment lines and in the setting of immunotherapy resistance, represents an important and innovative field of research. Moreover, to define new combined treatments incorporating radiotherapy or other locoregional therapies, including oncolytic viruses, it is essential to characterise immune-system changes during locoregional treatment according to the different treatment modalities and radiation fractionation schedules. Key enabling elements for the achievement of the objectives of this research line include the biobanking of tissue samples and biological fluids, digital pathology analyses, and novel models based on viable tissue macrosections and three-dimensional cultures. These data will be integrated with patients’ radiological and clinical information through a multidisciplinary approach involving radiologists, surgeons, pathologists, medical oncologists, radiation oncologists, immunologists, virologists, and molecular and computational biologists.

Objectives

The main objectives of this research line are: a) to identify TME-mediated pro- and antitumour immune mechanisms involved in resistance to immunotherapeutic treatments; b) to identify clinical and biological factors predictive of response to immunotherapy, as well as biomechanical signals involved in the modulation of the immune response; c) to perform immunoprofiling analyses and identify biomarkers derived from high-throughput assays; d) to define combinations of ICIs with vaccination strategies, gene therapy and radiotherapy; e) to define the role of viral infections in cancer; f) to identify therapeutic targets for the reactivation of antitumour immune responses.