The role of the epithelial cell immune modulation in the activation of systemic anti-tumour immune responses: Implications for Immunotherapy.
Peter Lawrence Smith has recently joined the ICVI as a postdoctoral research fellow. Peter studied for a PhD in innate and adaptive immunology at Queen Mary University of London and has previous postdoctoral experience working on vaccines for cancer and infectious disease. Peter’s interests include studying methods to improve anti-cancer vaccination, modulation of the immune response, the immunotherapeutic effects of chemotherapy and how to counter the tumour’s immune inhibitory properties.
Peter’s research for the ICVI is focused on three related areas. Effective immunotherapy requires the activation of important white blood cells called dendritic cells. These cells are capable of engulfing dying tumour cells and presenting the fragments to ‘killer’ T-cells which enables them to target tumour cells for destruction. Unfortunately the dendritic cells often fail to reach the tumour or are switched off in the tumour microenvironment. Part of Peter’s research involves investigating how to prime dendritic cells to improve their function and treating the tumour so that it attracts activated dendritic cells.
A related research project involves studying how the intestinal immune response regulates anti-tumour immunity. Recent studies have shown that the intestinal microbiome, the bacteria in our gut, have profound effects on the effectiveness of both immunotherapy and chemotherapy through modulating intestinal immunity. Currently it is unknown how the microbiome performs this role or how the mechanisms involved might be harnessed to improve cancer treatment. Peter is interested in manipulating the immune response in the intestine by stimulating intestinal epithelial cells which are known to play an important role in intestinal immunity. It is thought that modulating the signals the immune system receives from the intestinal epithelial cells will promote a systemic immune response capable of enhancing tumour immunotherapy. These desirable immune responses are probably mediated through the activation of both dendritic cells and T-cells.
In addition to these pre-clinical studies Peter is involved in studying the effectiveness of a novel cancer immunotherapy called IMM-101. IMM-101 is a mycobacterial adjuvant thought to be capable of priming anti-tumour immunity. IMM-101 is being studied in a phase Iia trial in combination with an established immunotherapy called ‘checkpoint inhibition’. Checkpoint inhibition is currently a first line therapy for metastatic Melanoma and works by stopping the tumour from switching off T-cells. However this therapy is not successful in all patients. We hypothesize that the addition of IMM-101 can increase the effectiveness of checkpoint inhibition by the general activation of anti-tumour immunity, probably mediated through the activation of dendritic cells.
Through the activation of dendritic cells, either by mycobacterial stimulation or modulation of intestinal epithelial cells, and by improving the immunogenicity of tumours whilst preventing the tumour from switching off T-cell responses with the use of checkpoint inhibition Peter hopes to improve tumour immunotherapy.