TRANSLATIONAL HEMATOLOGY AND IMMUNOLOGY

Principal Investigator

Staff

Research topic

Our core mission is to unravel the intricate mechanisms behind immune resistance in multiple myeloma (MM) and to identify novel immune targets for clinical translation. By means of collaborative efforts and training programs, we strive to ensure mentoring for the upcoming generation of scientists.

Background

An immunosuppressive bone marrow microenvironment poses a major obstacle in achieving long-lasting responses in MM. In this scenario, immunotherapy emerges as a promising avenue for investigation. Restoring immune competence is essential in countering the progressive dysfunction of innate and adaptive immune systems during MM progression. A comprehensive understanding of the mechanisms underlying immune escape in MM can reveal novel targets for immunotherapy, aiming to reinstate anti-tumor immune surveillance and extend patient survival.

Research achievements

Our lab research has been dedicated to exploring anticancer immune surveillance, focusing on the intricacies of immunogenic cell death (ICD) in MM, a cell death modality known for eliciting a potent and specific immune response against tumor antigens. The emerging understanding underscores that chemotherapy not only directly targets cancer cells but also renders them ‘visible’ to the immune system, reactivating anti-tumor immunity – a pivotal insight for MM treatment. Central to ICD is the release of damage-associated molecular patterns (DAMPs) by dying cancer cells, driving tumor cell phagocytosis by dendritic cells (DCs) and T cell priming. Our work revealed the proteasome inhibitor bortezomib inducing significant antitumor immune response in MM through the ICD pathway, mediated by the cGAS/STING innate immune response signaling. The evidence we provided supports the notion that this mechanism significantly contributes to the exceptional clinical benefits observed in MM patients following BTZ treatment. Further investigations highlighted a dysfunction in the ICD mechanism in high-risk MM patients with del(17p) and proposed a novel strategy to restore BTZ-induced immune activation in this subgroup. Building on these findings, we have underscored the fundamental role of the crosstalk between innate and adaptive immunity in orchestrating an efficient anti-MM immune response, highlighting the critical role of the phagocytosis in priming an effective anti-MM immunity.

Conclusions and perspectives

Building on these discoveries, our ongoing projects focus on unraveling tumor intrinsic mechanisms of immune evasion, with particular attention on the contribution of high-risk cytogenetic abnormalities to this process. This approach aims to identify novel immune targets for therapeutic interventions. Our lab is dedicated to translating preclinical discoveries into clinical applications by developing therapeutic strategies that promote immune activation and enhance immune control of MM. In parallel with our scientific mission, we are committed to fostering mentorship within our lab, supporting the next generation of scientists to contribute meaningfully to the ongoing advancements in the field.

Publications

At this link, you can find all the scientific publications of the Principal Investigator.