Project: The role of microbiota and short chain fatty acids in improving anti-cancer potential of killer T cells
Checkpoint inhibitors and adoptive T cell therapy have revolutionized the treatment of cancer. Nonetheless, the effectiveness of these therapies differs dramatically between patients and recent studies suggest that the microbiome of an individuum plays an important role in determining the responsiveness to T cell therapy (Gopalakrishnan et al. Science 2018; Routy et al. Science 2018). The effectiveness of checkpoint inhibitors is linked to CD8+ T cells with memory potential. We are therefore studying if a clinically-relevant relationship exists between microbiota and the capacity of effector CD8+ T cells to transition into memory cells. We found that effector CD8+ T cells required stimulation from a particular microbiota-derived short-chain fatty acid (SCFA) to acquire memory potential and that this SCFA can be used therapeutically to enhance memory potential of effector CD8+ T cells. Building on these novel insights, we are seeking a highly motivated PhD student with a B.Sc (Hons)/M.Sc degree to investigate if microbiota-derived SCFA promote the differentiation of CD8+ T cells that respond better to checkpoint inhibitors and have great capacity to kill tumours (Fig. 1). The objectives of the PhD project are (i) to delineate the underlying mechanisms of how SCFA promote memory potential in effector CD8+ T cells, (ii) identify microbiota sources of these SCFA and (iii) to apply these insights to the improvement of T cell therapy against different types of cancer
The Bedoui group uses models of viral and bacterial infections to study how the innate and the adaptive immune systems interact. Key foci are to understand how innate cells sense pathogens and how this information is integrated into T cell responses that control infections and cancer.