Mavilio Group

Clinical and Experimental Immunology Lab
  • Domenico Mavilio M.D., Ph.D. - Principal Investigator Clinical and Experimental Immunology View More

Innate Immunity is the very first line of defense against any invasion of the human body and represents the main research focus of our Unit of Clinical and Experimental Immunology (UCEI). We exploit innate immune responses in human pathologies with a particular focus on viral infections (HIV-1, HCMV, and SARS-CoV-2), hematologic malignances, solid gastro-enteric, brain, gynecological and thymic epithelial tumors, auto-immune and auto-inflammatory diseases and endothelial disorders. Our current research approach is based on translational human immunology with the involvement of both physician and scientists to fill the gaps and build a bridge between these two sides of modern medicine. Our research projects investigate the impact of Natural Killer (NK) cells, gamma delta (gd) T cells, Innate Lymphoid Cells (ILCs), Monocyte/Macrophages and Dendritic Cells (DCs) on the pathogenesis of human diseases. The UCEI has a full expertise in cell and molecular human immunology in association with advanced technologies such as multiparametric flow cytometry and bioinformatics approaches. The UCEI currently collaborates with several universities and research institutes in Italy, Switzerland, France, Spain, Germany Portugal, United Kingdom and Unites States. Our research is funded by Intramural programs of the Humanitas Research Hospital and the University of Milan as well as by competitive grants from Italian Ministry of Health, Fondazione Cariplo, Fondazione Umberto Veronesi, Associazione Italiana per la Ricerca sul Cancro (AIRC) and European Union.

Bioinformatician: Dr. Sara Terzoli, Ph.D. Student

Lab Technician: Dr. Anna Carletti

The main macro-areas of our research interest include:

A) Innate immune-reconstitution in patients with hematologic malignances undergoing haploidentical hemapoietic stem cell transplantation

Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) represents a therapeutic option to cure hematologic malignancies. The reconstitution of immune cells is key in determining a positive or negative clinical outcome of HSCT. Hence, a better understanding of the kinetic and quality of the immune-reconstitution following HSCT can predict and therapeutically target opportunistic infections, tumor-relapse, engraftment and the onset/degree of Graft versus Leukemia (GvL) effect as wells as Graft versus Host Diseases (GvHD).  We recently disclosed the kinetic of T, B and NK cell immune-reconstitution after haplo-HSCT. Therefore, we are now exploring different innate cellular populations, including Innate Lymphoid cells (ILCs) and gdT in relation to cytomegalovirus (HCMV) infection/reactivation inhaplo-HSCT. Moreover, we are focusing our intereston phenotypic, functional and molecular characterization of the recently discovered “memory-like” NK cell subset expanded in response to a HCMV reactivation and endowed with adaptive properties.Moreover, the disclosure of this NK cell subset will allow us to optimize/customize the haplo-HSCT procedure, to improve the clearance of residual tumor cells, decreasing graft rejection, GvHD and opportunistic infection onset.

Research Group:

Group Leader: Dr. Clara Di Vito, Ph.D. – Staff Scientist

Dr. Michela Calvi, Ph.D. Student

Dr. Alessandro Frigo, Ph.D. Student

Fathi Mohammed Ubahle, Master Degree Student

Erika Siano, Undergraduate Student

B) Characterization of innate cellular subsets in human solid tumors

Innate cellular populations including gd T cells, NK cells, ILCs and Dendritic cells (DCs) display a broad array of anti-tumor and pro-tumor functions by combining their rapid innate cytotoxic response with secretion of immunoregulatory cytokines. In collaboration with different clinical and surgery units in the metropolitan area of Milan, the UCEI runs several translational projects to perform comprehensive and comparative immune characterization of healthy and tumor-associated cells in both tissue and peripheral blood compartments of different human tumors such as colorectal carcinoma (CRC), primary and metastatic liver cancers and gynecological tumors. In particular, we aim to fully analyze phenotypic, functional and transcriptional anti-tumor profiles correlated to the patient-related clinical outcome such as tumor progression, response to treatment and number of metastases in order to develop new therapeutic cellular and molecular targets.

Research Group:

Group Leader: Dr. Joanna Mikulak, Ph.D. – Staff Scientist

Dr. Valentina Cazzetta, Ph.D. Student

Dr. Paolo Marzano, Ph.D. Student

Ahmed Darwish, Master Degree Student

C) Role of endothelial dysfunction in the pathogenesis of unprovoked venous thromboembolism and in antiphospholipid syndrome-associated thrombosis

Endothelial colony-forming cells (ECFCs) are bone-marrow-derived cells that play a crucial role in endothelial homeostasis and repair. The characterization of ECFCs isolated and cultured from the peripheral blood represents a non-invasive procedure for the functional assessment of the endothelial compartment. We recently demonstrated that ECFCs obtained from patients with unprovoked venous thromboembolism (uVTE) have impaired proliferative and vasculogenic activity that could be detrimental to the maintenance of endothelial integrity in vivo, and we also demonstrated that pathologic up-regulation of TNFSF15-TNFRSF25 axis may play a causative role in the onset of uVTE. In order to deepen comprehension of differential pathogenetic mechanisms sustaining unprovoked and provoked VTE (pVTE), we are now characterizing ECFCs obtained from both uVTE and pVTE patients to identify the molecular mechanisms involved in endothelial dysfunction (ED) in uVTE patients.
Finally, we recently extended the analysis of ED also to anti-phospholipid syndrome (APS)-associated thrombosis. Thanks to patient specific-ECFC characterization, we aim to: i) assess if ED in APS is only antiphospholipid antibodies-mediated or is also antiphospholipid antibodies-independent; ii) identify the molecular pathway(s) responsible for ED.

Research Group:

Group Leader: Dr. Francesca Calcaterra, Ph.D. – Staff Scientist

Dr. Assunta Cancellara, Ph.D. Student

Roberta Ciceri, Master Degree Student

D) Immune microenvironment in brain and thymic epithelial tumors and flow cytometry

This research line investigates on the immune infiltrate within high-grade glioblastoma and thymoma and thymic carcinoma to fully analyze phenotypic, functional and transcriptional anti-tumor profiles correlated to the patient-related clinical outcome such as tumor progression, response to treatment and number of metastases in order to develop new therapeutic cellular and molecular targets. Prof. Della Bella, has also a great experience and skills in flow cytometry and set up the more advanced methodologies in this field.

Research Group:

Group Leader: Prof. Silvia Della Bella, M.D., Ph.D. – Staff Scientist

Dr. Sara Franzese, Ph.D. Student

Dr. Simone Balin, Ph.D. Student

Martina Defendi, Master Degree Student

E) Targeting acute immune responses and aberrant inflammation to improve the clinical outcome of elderly SARS-Cov-2 infected patients

The disease progression in SARS-CoV-2 infected patients can be either asymptomatic or develop life-threatening pneumonia and respiratory insufficiency. While the former appears to resolve spontaneously, the latter require hospitalization and the frequent use of mechanical ventilation in intensive care units. The reasons of this dichotomy are still unknown and must be somewhat linked to the different degrees of immunity response. Therefore, a better understanding of magnitude, specificity and kinetics of anti–SARS-CoV-2 immune response is crucial to the treatment of SARS-CoV-2 infected patients. For these reasons, in our study of translational immunology we aim to disclose the impact of SARS-CoV-2 acute infections and of the related biologic treatments on the homeostasis of those immune cells naturally endowed with the highest antiviral activities: Natural Killer (NK) cells, gd T lymphocytes, Dendritic cells (DCs), and neutrophils. In particular, we will characterize their effector-functions in association with the clinical outcome of SARS-CoV-2 acutely infected patients with different sex, ages and disease progression. In fact, the main focus of our study is to target acute immune responses and aberrant inflammation to improve the clinical outcome of elderly patients as they represent the most fragile cohort of patients showing the highest rates of morbidity and mortality.

    Selected Publications

  • Domenico Mavilio Publications

    1)   Mavilio D. *, J. Benjamin, M. Daucher, G. Lombardo, S. Kottilil, M.A. Planta, E. Marcenaro, C. Bottino, L. Moretta, A. Moretta, and A.S. Fauci. Natural Killer cells in HIV-1 ...

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