FRANCESCA NAZIO, PHD
Ospedale Pediatrico Bambino Gesù
CureSearch Young Investigator Award: 2022-2025
Project title: Targeting autophagy to boost the immune response against medulloblastoma
Approximately 18% to 20% of childhood brain tumors are medulloblastoma, making it the most common cancerous brain tumor in children. Most medulloblastomas occur in children under 16. More than 70% occur in children younger than 10. Survival in the most high-risk subtype of medulloblastoma, Group 3 medulloblastoma, ranges from 39% in infants to 50% in children. The tumor location as well as current treatments affect brain development causing neurological, neuropsychological, and physical disabilities – even into survivor adulthood.
Francesca Nazio, PhD, is a CureSearch Young Investigator conducting research at the Bambino Gesù Children’s Hospital to disrupt a process in medulloblastoma cells that not only promotes their survival but also enables them to escape anti-tumor immune responses. Natural killer (NK) cells, a part of the immune system, can target and destroy tumor cells. NK cells target medulloblastoma cells by attaching to proteins on the surface of the cancer cells. The ability of medulloblastoma to avoid detection by NK cells may be a mechanism by which medulloblastoma evades anti-tumor immune responses. Dr. Nazio aims to redirect homing of NK cells to medulloblastoma to reactivate the anti-tumor immune response. She will do so by blocking a process called autophagy. Cancer cells use the process of autophagy (self-eating) to survive even when nutrients are low and they receive signals to die. In addition to promoting cell survival, autophagy plays a role in deadening the immune response. Dr. Nazio proposes a novel concept in medulloblastoma immunotherapy that would bypass the harmful effects of traditional radiation and chemotherapy treatments by applying NK cell-mediated immunotherapy in combination with a therapeutic that stops the process of autophagy for the treatment of high-risk medulloblastoma. She hypothesizes that combining a drug that halts autophagy with an immunotherapy will offer a safer and more effective treatment for medulloblastoma than traditional radiation and chemotherapy.
Project Update: In 2022, the team performed co-culture experiments using both medulloblastoma cell lines and patient-derived cells in the presence of Natural Killer (NK) cells isolated from healthy donors to assess NK-mediated MB cytotoxicity after autophagy manipulation. Dr. Nazio also received a grant from the Italian Association for Cancer Research that supports the transition of young investigators, and published a review publication giving an update of the latest findings about metabolic reprogramming (including autophagy-related processes) in medulloblastoma and the possible complex mechanism of modulation.