Grant: Project Grant

Immune checkpoint blockade therapy (ICBT) is a very promising anti-cancer strategy that harnesses the therapeutic potential of the immune system. ICBT is now successfully used in a wide range of human cancers and has revolutionized the treatment of cancer. Despite this, individual responsiveness to ICBT varies widely and many individuals also develop severe immune-related toxicity following ICBT. Although several factors have been associated with responsiveness to ICBT and the downstream toxicity, recent data strongly supports a role for the gut microbiome. This is exciting because, in contrast to many other factors, the gut microbiome has the potential to be modified. We have identified specific bacterial species and a bacterial-derived small molecule that play a critical role in promoting the efficacy of ICBT in multiple mouse models of cancer. In this research project, we will further identify the cellular and molecular pathways involved in promoting ICBT responsiveness whilst also protecting from adverse toxic events. We will also examine the role of human-derived bacteria in controlling the efficacy of ICBT. The overall goal will be to develop targeted and defined microbial therapeutics to be used as an adjuvant therapy to ICBT.