Natalie Gatteno
Pronouns: She/Her
Research Mentor(s): Anutosh Ganguly
Research Mentor School/College/Department: Surgery / Medicine
Program: UROPF
Session: Session 3 (11:00am – 11:50am)
Authors: Natalie Gatteno, Aunutosh Gaungly, Brian Song, Katherine Buglak, Ashley Ortenburg, Clifford Cho
Abstract
A study was conducted to investigate systemic immune response after treatment with a tumor ablation therapy called Histotripsy (Ht) on the tumor of the abscopal side of treatment in mice. In this experiment, we hope to uncover the best results of Ht to ensure pre-clinical optimization. A bilateral flank tumor model was established using B16 F10 cell lines that have been genetically modified to express the GP33 peptide. Preliminary results have shown that post Ht culminates in a systemic tumor-specific immune response. Abrogation of hypoxia after Histotripsy in the treated tumor has been found to be one of the underlying mechanisms. The immune response in the abscopal side was notable, but insufficient to provide a long-term benefit. Our preliminary result indicated that substantial CXCR4+ Treg cell infiltration correlated with marginal immunotherapeutic benefit in the abscopal side. We hypothesized that the activation of the CXCL12:CXCR4 axis in the abscopal site as a consequence of hypoxia is responsible for dampened immune response. Due to having found that the abscopal side always has hypoxic conditions post Ht, we plan to dampen the CXCL12:CXCR4 axis of immunosuppression by suppressing Hif response. Therefore we have used pharmacological intervention by Hif inhibitor to dampen the CXCL12:CXCR4 axis to strengthen the immune therapeutic benefit of the abscopal site by Hif abrogation.
