Research Group

Mavilio Group

Clinical and Experimental Immunology Lab

Mavilio Group

Domenico Mavilio

Group Leader

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 challenge

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.

Selected publications

Carenza C
Front Immunol
Perioperative corticosteroid treatment impairs tumor-infiltrating dendritic cells in patients with newly diagnosed adult-type diffuse gliomas.
van Beek JJP
Blood Adv
Selected memory T cells infused post haploidentical hematopoietic stem cell transplantation persist and hyper-expand.
Bruni E
J Immunother Cancer
Intrahepatic CD69(+)Vδ1 T cells re-circulate in the blood of patients with metastatic colorectal cancer and limit tumor progression.
Di Vito C
Front Immunol
Natural Killer Cells in SARS-CoV-2 Infection: Pathophysiology and Therapeutic Implications.
Calvi M
Front Immunol
Development of Human ILCs and Impact of Unconventional Cytotoxic Subsets in the Pathophysiology of Inflammatory Diseases and Cancer.
Cazzetta V
Cell Rep
NKG2A expression identifies a subset of human Vδ2 T cells exerting the highest antitumor effector functions.
Van Beek JJP
Haematologica
Single-cell profiling reveals the dynamics of cytomegalovirus-specific T cells in haploidentical hematopoietic stem cell transplantation.
Zaghi E
JCI Insight
Single-cell profiling identifies impaired adaptive NK cells expanded after HCMV reactivation in haploidentical HSCT.
Cazzetta V
Cancers (Basel)
Natural Killer-Dendritic Cell Interactions in Liver Cancer: Implications for Immunotherapy.
Mariotti J
Blood Adv
Impact of donor age and kinship on clinical outcomes after T-cell-replete haploidentical transplantation with PT-Cy.
Della Bella S
Cardiovasc Res
Pathologic up-regulation of TNFSF15-TNFRSF25 axis sustains endothelial dysfunction in unprovoked venous thromboembolism.
Mikulak J
Nat Immunol
HIV-1-induced inflammation shapes innate immunity and induces adaptive traits in NK cells.
Mikulak J
JCI Insight
NKp46-expressing human gut-resident intraepithelial Vδ1 T cell subpopulation exhibits high antitumor activity against colorectal cancer.
Bruni E
J Immunother Cancer
Chemotherapy accelerates immune-senescence and functional impairments of Vδ2(pos) T cells in elderly patients affected by liver metastatic colorectal cancer.
Roberto A
Haematologica
The early expansion of anergic NKG2A(pos)/CD56(dim)/CD16(neg) natural killer represents a therapeutic target in haploidentical hematopoietic stem cell transplantation.
Donadon M
J Gastrointest Surg
Increased Infiltration of Natural Killer and T Cells in Colorectal Liver Metastases Improves Patient Overall Survival.
Calcaterra F
J Invest Dermatol
Increased Frequency and Vasculogenic Potential of Endothelial Colony-Forming Cells in Patients with Kaposi’s Sarcoma.
Mikulak J
Retrovirology
Impact of APOL1 polymorphism and IL-1β priming in the entry and persistence of HIV-1 in human podocytes.
Hudspeth K
J Autoimmun
Human liver-resident CD56(bright)/CD16(neg) NK cells are retained within hepatic sinusoids via the engagement of CCR5 and CXCR6 pathways.
Roberto A
Blood
Role of naive-derived T memory stem cells in T-cell reconstitution following allogeneic transplantation.
Cappelletti M
Immunology
Bright expression of CD91 identifies highly activated human dendritic cells that can be expanded by defensins.
Roberto A
Bone Marrow Transplant
B-cell reconstitution recapitulates B-cell lymphopoiesis following haploidentical BM transplantation and post-transplant CY.
Hudspeth K
Blood
Engagement of NKp30 on Vδ1 T cells induces the production of CCL3, CCL4, and CCL5 and suppresses HIV-1 replication.
Correia DV
Blood
Differentiation of human peripheral blood Vδ1+ T cells expressing the natural cytotoxicity receptor NKp30 for recognition of lymphoid leukemia cells.

Group members

Mavilio Group
Francesca Calcaterra

Staff scientist

Mavilio Group
Michela Calvi

PhD student

Mavilio Group
Assunta Cancellara

PhD student

Mavilio Group
Anna Carletti

Technician

Mavilio Group
Valentina Cazzetta

PhD student

Mavilio Group
Roberta Ciceri

PhD student

Mavilio Group
Silvia Della Bella

Associate professor, University of Milan

Mavilio Group
Clara Di Vito

Staff scientist

Mavilio Group
Sara Franzese

PhD student

Mavilio Group
Alessandro Frigo

PhD student

Mavilio Group
Domenico Mavilio

Group Leader

Mavilio Group
Joanna Mikulak

Staff scientist

Mavilio Group
Sara Terzoli

PhD student
Bioinformatician