Abstract 5894: Changes in the gut microbiota associated with oncolytic virotherapy efficacy in a gastric cancer murine model

Gastric cancer is the third leading cause of cancer-related mortality worldwide, and current standard-of-care treatment allows for a 5-year survival rate of 20%. Newer treatments against solid tumors include an oncolytic adenovirus armed with T-cell activator OX40L, named Delta-24-RGDOX, which expresses the positive immune checkpoint OX-40L. While studies have revealed the interaction between the gut microbiome and immunotherapy agents, it’s still unknown how the gut microbiome might influence viroimmunotherapy efficacy. We hypothesized that the gut microbiota plays an important role in modulating the virus-driven anti-tumor response. To test this hypothesis, immunocompetent C57BL/6 mice were subcutaneously implanted M12Luc gastric cancer cells and were administered PBS (control) or Delta-24-RGDOX by intratumoral injections. Mice fecal pellets were collected at three different time points: (1) before tumor implantation, (2) after tumor establishment, and (3) 14 days after the first dose of the treatment. Genomic DNA was isolated with the QIAGEN DNeasy Powersoil Kit from fecal pellets of cancer-bearing mice (n=60), and the V4 region of the 16S ribosomal RNA gene (prokaryotes) was sequenced using the Illumina platform. Data was deposited in QIITA for quality assessment, followed by microbial community analysis using the taxonomic reference database SILVA and the downstream platforms QIIME2 and R with a rarefaction depth of 9,187 reads per sample. We found significant differences in the gut microbiome community structure of viroimmunotherapy-treated mice compared to controls (ANOSIM p-value=0.025). No differences in gut diversity were observed, although control animals tended to show higher richness (Kruskal-Wallis p-value>0.05). Of interest, the bacterial composition of responders to the viroimmunotherapy had a decrease in Actinobacteria and an increase of Patescibacteria. Additionally, responders had higher levels of butyrate-producer bacteria such as Ruminococcaceae and Clostridium sensu stricto. These findings suggest that butyrate producers may be important in regulating host gut homeostasis associated with the clinical efficacy of Delta-24-RGDOX, suggesting possible benefits of microbiota modulation in patient survival. This project was sponsored by a pilot award within The University of Puerto Rico/University of Texas MD Anderson Cancer Center (MDACC) Partnership for Excellence in Cancer Research Grant (2U54CA096297-16). Citation Format: Natalie M. Mel