Skyler Bufalini
Pronouns: she/her
Research Mentor(s): Anutosh Ganguly
Research Mentor School/College/Department: Surgery / Medicine
Program:
Authors: Allison Bontrager, Brian Song, Natalie Gatteño, Kathrine Buglak, Skyler Bufalini, Anutosh Ganguly, Clifford Cho
Session: Session 6: 3:40 pm – 4:30 pm
Poster: 11
Abstract
Previous studies from our group have demonstrated the efficacy of Histotripsy in achieving non-thermal tumor ablation. This non-invasive technique employs focused ultrasound pulses to mechanically disrupt cellular and subcellular structures, resulting in the release of tumor antigens while preserving their immunogenicity. Histotripsy triggers DAMP release and necroptosis, accompanied by immunogenic cell death transcriptional responses in tumor cells, as well as innate immune activation transcriptional responses in infiltrating myeloid and natural killer (NK) cells. Moreover, the delayed intratumoral infiltration of CD8+ T cells was found to align spatiotemporally with features of ferroptosis in cancer cells. The current study advances the notion that Histotripsy-induced necroptosis initiates a spectrum of physiological changes within the tumor microenvironment conducive to immunostimulatory effects. Our investigation underscores the crucial role of necroptosis in eliciting an optimal tumor-specific cytotoxic T-cell response. Inhibition of necroptosis, achieved through the administration of Necrostatin in B16F10 flank melanoma tumors post-histotripsy, effectively prevents the delayed cytotoxic CD8+ T cell response. Additionally, our findings reveal that modifying Histotripsy parameters to influence cell death pathways other than necroptosis also impacts the optimal cytotoxic T-cell response. In summary, our research posits that necroptotic cell death induced by Histotripsy is a prerequisite for achieving optimal immune activation, and subsequent cytotoxic T-cell response
