Abstract B008: PD-1/PDL-1 blockade remarkably regulates abundance of gut commensal microbiota in a murine syngeneic tumor model

Abstract

Abstract Microbiota has been linked to immune surveillance of tumor progression and tumor growth in cancer patients as well as in cancer mouse models. Recent research reveals that gut microbiota has the potential to act as a biomarker to predict responders or even as an alternative treatment approach. Therefore, several gut microbes discovered in this invention (e.g., Akkermansia, Adlercreutzia, Coprococcus) could possibly be used as a biomarker to predict PD-1 antibody efficacy or could combine with PD-1 antibody in preclinical and clinical settings. Considering the complexity of intestinal microorganisms, a larger panel or wider spectrum of microbiota species may be involved in this process. The current study was designed to explore the possibilities of identifying multiple strains of intestinal microbiota that may be involved in antitumor effects of immune-checkpoint inhibitors, using preclinical tumor models. Gut microbiota changes were determined before and after a series of anti-PD-1 mAb treatments had been administered. Sixteen-S (16S) rRNA-seq was performed using feces collected at 4 time points. The results indicate that significant antitumor activity was found to be associated with gut microbiota changes of a large panel of microbiota, including a few strains with robust upregulation or downregulation. Upon further characterization and confirmation, these findings could lead to identification of one or more microbiota strains that could have biomarker potentials for cancer immunotherapy. Citation Format: WenQing Yang, Jian Ding, Xiangchao Gu, Fei Chen, Juan Zhang, Qian Shi. PD-1/PDL-1 blockade remarkably regulates abundance of gut commensal microbiota in a murine syngeneic tumor model [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr B008.