Giorgio Trinchieri's research through the years has mostly focused on innate immunity within infections, cancer, cancer inflammation and human immunology. Major achievements include seminal contributions to NK cell characterization and biology, discovery of plasmacytoid DC, discovery of Interleukin-12, and demonstration that microbiota impacts inflammatory and immune responses to cancer and cancer chemo- and immune-therapy.
Trinchieri originally described the specificity of allogeneic cytotoxic T cells for class-I MHC and cross-presentation and class-I MHC restriction of tumor antigens. In a series of papers in 70s-80s, Trinchieri contributed to the original characterization of human NK cells, described their role as innate producers of cytokines, identified type I IFNs as major activators of NK cells and discovered a new human cell type, now called plasmacytoid DC, as a major source of type I IFN in response to viruses. Trinchieri went on to identify the mouse counterpart of human plasmacytoid DC, paving the way for study their function in experimental mouse models of infections and tumors. In the 80’s-90’s Trinchieri identified IL-12, a novel cytokine capable activating NK cells and demonstrated its impact in innate immunity, Th-1 cell polarization, host responses to pathogens, cancer, and hematopoiesis. His discoveries of pDCs and IL-12 were among the original observations defining the link between innate resistance and immunity. Recently, Trinchieri focused on the impact of cytokines and inflammation in cancer. In this field, he has demonstrated the importance of intestinal microbiota in influencing inflammatory and immune responses to cancer and anti-cancer chemo and immune therapy in mouse models as well as in observational and interventional clinical studies. His work has established the ability of fecal microbiota transplant to improve the response to anti-PD1 therapy in a proportion of anti-PD1 refractory melanoma patients, has demonstrated the important role of dietary fibers in favoring response to anti-PD1 therapy in melanoma patients and has contributed to identify the bacterial species able to favor or impede anti-PD1 therapy in patients and their mechanism of action.