Immunology, Transplantation and Infectious diseases
Tumor immunology
Pancreatic cancer is an aggressive disease with dismal prognosis, with the majority of patients diagnosed with advanced disease. Chemotherapy is standard of care after surgery and in locally-advanced and metastatic disease with a still largely disappointing overall 5-year survival rate (7-8%). In the last years, immunotherapy has substantially improved patients’ survival in several neoplastic diseases. However, immunotherapy has shown little or no clinical impact in pancreatic cancer, possibly due to its highly immunosuppressive tumor microenvironment. In addition to cytostatic/cytotoxic effects, chemotherapy has been proposed to induce de novo immune responses and/or remodeling of existing tumor-targeting immunity. How chemotherapy in pancreatic cancer impacts the tumor microenvironment and whether chemotherapy-induced changes may help in devising novel immunotherapeutic strategies is not completely elucidated.
Research activity
We hypothesize that the pathways targeted so far by immunotherapy may not be the dominant ones in pancreatic cancer, and the expression of targetable activation/exhaustion markers may be modified by chemotherapy received prior or in combination with immunotherapy. Thus, better characterization of immune cells, and their expressed inhibitory receptors, present in patients' sample untreated or treated with chemotherapy is warrant.
Aims of our research are: i) to investigate the immune contexture in the blood and neoplastic tissues of pancreatic cancer patients with primary and metastatic tumors, and ii) to identify targetable immunomodulatory effects, unique to pancreatic cancer, induced by chemotherapy.
To these aims, we set clinical and experimental pipelines in collaboration with surgeons and clinical oncologist in the hospital. Blood and neoplastic tissues are collected (also in the framework of a collaborative program within the Institution funded by AIRC) from patients with primary tumor either untreated or treated with neoadjuvant chemotherapy, and patients with liver metastases. Analyses performed comprise: i) high-dimension flow cytometry with antibody panels allowing detection of cells of the innate and adaptive immunity in blood and tissues, ii) bulk RNAseq on primary tumor tissues of untreated and treated patients with bioinformatic analyses to identify immune cell subsets by deconvolution tools and of differentially expressed genes and pathways in the different conditions, iii) spatial proteomics on primary tissue samples and biopsies of liver metastases.
