Abstract 1264: Commensal microbiota is involved in anti-PD-1 mAb-mediated antitumor activity in a preclinical tumor model

Abstract

Abstract Background: A number of studies have shown that the gut microbiome may influence anti-tumor immune responses via innate and adaptive immunity, and the recent work in mice has highlighted the key roles of the gut microbiota in mediating tumor responses to chemotherapeutic agents and immunotherapies targeting PD-L1, PD-1 or CTLA-4. Multiple studies have demonstrated that the gut microbiome can markedly influence the outcome of PD-1 blockade in mice and patients and several commensal have been proved to be associated with favorable clinical outcome. Considering complexity of intestinal micro-organisms, a larger panel or wider spectrum of microbiota species maybe involved in this process. Methods: Since compositional differences in the microbiome may influence cancer development and responses to therapies, we sought to determine whether intestinal bacterial composition and abundances of the tumor bearing mice were associated with a specific treatment outcome of immunotherapy. To test this, we analyzed and compared an enrichment of intestinal microbiota of CT26 syngeneic tumor bearing mice before and after a series of anti-PD-1 mAb treatment were given. Results The results demonstrating that some strains were robustly enriched and this enrichment was associated with tumor response to anti-PD 1 therapy, while as other strains were down regulated upon the checkpoint blockade. Conclusions: Upon further characterization and confirmation, these intriguing findings could lead to identification of one or more microbiota strains that could have biomarker potentials or therapeutic values for cancer immunotherapy. Citation Format: Fei Chen, Jian Ding, Xiangchao Gu, Juan Zhang, wenqing Yang, Qian Shi. Commensal microbiota is involved in anti-PD-1 mAb-mediated antitumor activity in a preclinical tumor model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1264.