RESEARCH GROUP

Domenico Mavilio

  • 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 and HCMV), hematologic malignances, solid gastro-enteric and brain tumors, viral infections, 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.

Laboratory Manager: Gianmarco Spata

Bioinformatician: Sara Terzoli

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. Elisa Zaghi, Ph.D. Student

Dr. Michela Calvi, Ph.D. Student

B) Characterization of innate cellular subsets in human solid tumors

 Innate cellular populations including gdT 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. 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, Predoctoral Fellow

C) Venous Idiopathic Thromboembolism

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. This research line assesses whether ECFCs may act as lymphatic endothelial progenitor cells in order to disclose the mechanisms underlying physiological and pathological lymphangiogenesis, as occurring in cancer microenvironment.

Research Group:

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

Dr. Assunta Cancellara, Ph.D. Student

D) Immune microenvironment in brain cancer and flow cytometry.

This research line investigates on the immune infiltrate within high-grade glioblastoma 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. Claudia Carenza, Ph.D. Student

Dr. Sara Franzese, Predoctoral Fellow

    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 ...

Group Members