Experimental Immunopathology Lab
We study humoral innate immunity and the regulation of inflammatory responses, with a special focus on two molecules we have co-discovered – the long pentraxin PTX3, the receptor IL-1R8 – and the complement system, with the final aim of developing new therapies and diagnostic/prognostic markers in cancer and infectious diseases.
The inflammatory response is a complex and diverse pathophysiological reaction activated when healthy tissues are wounded by physical or chemical stimuli, invaded by pathogens or damaged by toxins. The response is a chain-reaction engaging hundreds of different molecules (some of which evolved more than 500 million years ago) that recruits immune cells to the site of the damage to clear it from pathogens and diseased cells and to promote healing. Its activation is fundamental to fight off infections and eliminate cancer cells, but it can also – conversely – contribute to tissue damage and support tumor growth. Understanding the role played by these molecules and translating them to the clinic has tremendous implication for our ability to treat infections, cancer and immune-mediated diseases.
Main research areas
PTX3 as a paradigm of humoral innate immunity
The laboratory contributed to define and characterize a soluble mediator of the innate immune response, the long pentraxin PTX3, a molecule involved in the recognition of pathogens and inflammation. We characterized the biological activity of the long pentraxin PTX3 in the regulation of inflammatory responses to pathogenic microorganisms, tissue damage and cancer, focusing on its interplay with the complement system. In recent studies, we also demonstrate the prognostic potential of PTX3 as a strong independent predictor of 28-d mortality in Covid-19 patients.
IL-1R8: a checkpoint molecule of the IL-1 system
IL-1R8 is a negative regulator of inflammatory responses involved in different pathological conditions, from infections and inflammation to autoimmunity and cancer. IL-1R8 acts as a novel immune checkpoint in NK cells: we showed that unleashing NK cells by genetic inactivation of IL-1R8 resulted in inhibition of liver carcinogenesis and protection against liver and lung metastasis, as well as viral infections. These results opened a new line of research on the role of IL-1R8 in CD8+ T cells against cancer.
Complement and cancer
Flow cytometry, transcriptional analysis of tumor infiltrating leukocytes and in vivo experiments showed that the complement represents a key component of cancer-related inflammation promoting tumor growth: its deficiency is associated with reduced accumulation and functional skewing of tumor-associated macrophages, increased T-cell activation and response to anti-PD-1 therapy. Our results suggested that the lectin pathway and C3a–C3aR axis are key players in macrophage-mediated sarcoma promotion and immunosuppression.