Programma MD-PhD della Scuola di Medicina

Molecular basis of the interaction between tumor cells and the surrounding microenvironment in acute myeloid leukemia and multiple myeloma. Instructor prof. Ada Funaro

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Programma

Acute myeloid leukemia (AML) and multiple myeloma (MM) are prototypic diseases in which tumor cells educate the local microenvironment to support their growth, elude immune surveillance, and acquire resitance to therapy.

CD38 is highly expressed by MM plasma cells and CD38-targeted therapy is emerging as one of the most effective passive immunotherapy ever developed in MM. CD157 is expressed by AML blasts and is a promising target for immunotherapy. A phase I clinical trial with a novel defucosylated, humanized monoclonal antibody is currently on going. Beside tumor cells, CD38 is expressed on immune effector cells (NK cells, cytotoxic T cells, B cells, Vγ9Vδ2 T cells) and inhibitory cells such as, Tregs and myeloid-derived suppressor cells (MDSC), while CD157 is expressed by mesenchymal stromal cells, vascular endothelial cells and MDSC.

To understand the molecular basis of the interaction between AML and MM cells and the surrounding microenvironment, we exploit cellular and molecular approaches to study i) the role of CD38 and CD157 NAD-metabolyzing ectoenzymes in the control of neoplastic progression and evasion from immune response against the tumor, and ii) the anti-tumor activity of MHC-unrestricted immune effector cells in the microenvironment. Moreover, iii) we evaluate the direct or indirect impact of anti-CD38 and anti-CD157 targeted therapy on tumor cells, immune effector cells and stromal cells.

The final aim of our research is to disrupt the molecular mechanisms that keep tumor cells in their protective microenvironment making them susceptible to chemotherapy or immune attack.

Attività di supporto

Co-workers. Massimo Massaia, Erika Ortolan, Yuliya Yakymiv.

Note

Progetto del Corso Basi molecolari delle Terapie mirate per la cura del cancro

Scientific qualification of the PI: Entrez-PubMed Link to publications of prof. Funaro

Laboratory/Clinical Division, Department, Address, contacts

Laboratory of Immunogenetics; Department of Medical Sciences, Via Santena 19, 3^th floor.

In collaboration with: Hematology Division, AO S. Croce e Carle, Cuneo, Italy

Contacts:

Ada Funaro

Phone: (+39) 011-670-5991 (Lab)
Phone: (+39) 011-696-1734 (office)
E.mail: ada.funaro@unito.it

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