Clinical and Experimental Immunology Lab
In our translational research lab, we study and exploit mechanisms of innate immunity to design new therapeutic strategies against different human pathologies, with a particular focus on viral infections, blood and solid tumors, immune-mediated and endothelial disorders.
The mission of the immune system is to protect us from diseases. But we now know that it plays a key role or as a direct triggering cause or as a supporting actor. This is especially true for the innate immune system, a group of cells and molecules that coordinates first-line, quick and mostly unspecific responses to insults. The same innate immune players are implicated in chronic infections and collateral damage, sustain tumor growth and attack our tissues producing immune-mediated or endothelial disorders. Understanding these mechanisms will allow us to control and re-educate innate immunity when it goes off track.
Main research areas
Understanding the impact of the immune-reconstitution on the hematopoietic stem cell transplantation outcome
Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) represents a curative option for patients affected by hematologic malignancies. The comprehension of the kinetic and quality of T, B, Natural Killer (NK) cells, gamma delta (gd) T cells and Innate Lymphoid cells (ILCs) immune-reconstitution following haplo-HSCT could predict and therapeutically target opportunistic infections and Graft versus Host Disease, that frequently affect patients receiving a haplo-HSCT, while favoring the graft versus leukemia effect, thus improving the clearance of residual tumor cells.
Innate immunity in the microenvironment of human cancers
Innate immune cells can exert a broad array of anti-tumor functions. Unfortunately, their activity is impaired by the immune suppressive effects of the tumor microenvironment. A numerical, phenotypical, functional and transcriptional characterization of gd T cells, Dendritic Cells (DCs), NK cells and ILCs in different human solid and hematologic tumors will improve our understanding of their role in cancer development and progression and to implement strategies of cancer immunotherapy. In collaboration with the Humanitas Cancer Center, we are characterizing innate cells in liver metastatic colorectal cancer, hepatocarcinoma, gynecological cancers, high-grade glioblastoma, thymoma and myelodysplastic syndromes.
Endothelial progenitor cells in human health and disease
Endothelial colony-forming cells (ECFCs) are bone-marrow-derived cells that play a crucial role in endothelial homeostasis and repair. The characterization of ECFCs represents a valuable tool for non-invasive assessment of the endothelial compartment. We already demonstrated that ECFCs isolated from the blood of patients with unprovoked venous thromboembolism have impaired proliferative and vasculogenic activity and are characterized by the pathologic up-regulation of TNFSF15-TNFRSF25 axis. By studying them and including in the study also patients with secondary VTE, we are identifying novel molecular mechanisms involved in endothelial dysfunctions. Moreover, we recently extended the analysis of ED also to anti-phospholipid syndrome (APS)-associated thrombosis to study the role of ED also in this pathological setting.
Innate immunity in SARS-CoV-2 infection and vaccination
The disease progression of SARS-CoV-2 infection can be either asymptomatic or develop into life-threatening pneumonia. The reasons for this dichotomy are still unknown but are partly due to the profile of the patient’s immune response, therefore a better understanding of its magnitude, speciﬁcity and kinetics is crucial to the treatment of Covid-19 patients. For these reasons, we are studying the impact of both SARS-CoV-2 infection, in the acute phase and its neurological and neuropsychological complications (NeuroCOVID), and upon vaccination on the homeostasis of immune cells naturally endowed with the highest antiviral activities: NK cells, unconventional T cells (gd T cells and MAIT cells) and DCs.