Evento

The dual face of monocytes in cancer immunity

Il 20/10/2017 ore 14.30 - 15.30

Sala Conferenze, Via P. Castellino, 111 80131 Napoli

Vincenzo Bronte, from the Department of Medicine, University Hospital of Verona, wil give a seminar on Myeloid-derived suppressor cells (MDSCs) that are characterized by their myeloid origin, heterogeneous cell composition and ability to regulate negatively adaptive and innate immune responses to cancer. Their presence and frequency in the blood of cancer patients is emerging as a potential prognostic marker to monitor clinical outcome and response to therapy. Among different subsets, monocytic (M)-MDSC are extremely susceptible to low dose chemotherapy, to the point that administration of different agents can increase the efficacy of adoptive cell therapy with tumor antigen-specific CD8+ T cells by eliminating in vivo the immune suppressive M-MDSCs. Although endowed with different mechanisms of cell damage, the chemotherapeutic agents effective on M-MDSCs share the ability to down-regulate the expression of the same anti-apoptotic molecule. Surprisingly, not only M-MDSCs are poisoned and need to express this protein for their survival but the very same molecule regulates a complex transcriptional program. Human monocytes infected with lentiviral vectors expressing this apoptotic regulator modulated different genes including IDO1, PD-L1, PD-L2, IL-10, and IL-4Rα. Moreover, this enforced expression generated strongly suppressive MDSCs, able to inhibit both in vitro and in vivo T cell activation and proliferation, as well as control the severity of established graft versus host disease in xenogenic mouse models. The connection between apoptosis regulation and immune modulation was further exploited in transgenic mice that constitutively express an active form of the gene in the myeloid cell lineage. This novel, unexpected link between apoptosis and immune regulation in monocytes can have potential applications for the development of immune regulatory and cell-based therapeutic strategies, as well as representing a biomarker for cancer patients.

Vincenzo Bronte is currently Head of the Immunology Section in the Department of Pathology and Diagnostics of Verona University. He is full professor of Immunology in Verona University.
He was awarded in 2007 by the Accademia Nazionale dei Lincei (Rome, Italy) in 2008 by the Italian Foundation for Cancer Research for his oncology researchers. Bronte’s major achievements is the definition and molecular characterization of immunoregulatory cells, now called myeloid-derived suppressor cells (MDSCs), whose negative influence on antitumor immunity represents an obstacle to a successful immunotherapy of cancer.

Organizzato da:
Cnr - Istituto di biochimica delle proteine

Referente organizzativo:
Paola Italiani
Cnr - Istituto di biochimica delle proteine
Via P. Castellino, 111 80131 Napoli
p.italiani@ibp.cnr.it

Modalità di accesso: ingresso libero