Mechanisms of microbial immunomodulation in cancer immunotherapy.

Substantial data are building that the success of cancer therapy is impacted by the commensal microbes that live in or on the human body. This has been particularly relevant in the case of immune checkpoint blockade therapies, for which microbial characteristics associated with anti-cancer efficacy and treatment-related toxicity have been made [1-2]. Although clear links to gut microbiota were demonstrated, individual studies in the field have produced inconsistent results, raising questions about whether individual microbes, communities, their functionality or biochemical potential are the true mediators of the observed effects. Currently, this project explores commensal microbiota (mainly gut) in differing conditions of anti-cancer treatment response and toxicity through metagenomics and metabolomics. It interfaces with the group's broader aims of understanding how patient- or environment-level factors (e.g. sex hormones, body composition, diet) interact with traditional cancer cell or tumour microenvironment factors, to establish a more multidimensional understanding of measurable or modifiable factors in cancer immunotherapy. Future directions for this project include pre-clinical studies attempting to identify the most clinically impactful microbial fractions on immunotherapy response, and test whether specific response/toxicity-associated chemicals identified from metabolomic profiling of patient blood can causally reproduce the clinical associations observed in patients. 1. Science. 2018 Jan 5;359(6371):97-103. doi: 10.1126/science.aan4236. 2. Nat Med. 2021 Aug;27(8):1432-1441. doi: 10.1038/s41591-021-01406-6.