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Directing T-Cell Immune Responses for Cancer Vaccination and Immunotherapy

22nd December 2022

The COVID-19 pandemic disproportionally effects cancer patients and those at risk of cancer, who may also require repeated vaccination. However recent studies indicate that existing COVID-19 vaccines fail to prevent infection and that variants have emerged to which the vaccines are less effective. We’ve used our experience studying anti-tumour CD8+ T-cell responses to identify and test conserved and immunogenic regions of SARS-CoV-2, the virus responsible for causing COVID-19. These regions represent potential targets to improve COVID-19 vaccines. This research has been published in the Journal of General virology which has described the study as ‘a valuable and interesting contribution to the field as well as a useful resource for future vaccine research’.

We have completed our study on the effects of short chain fatty acids on immune function. We have found that SCFA, derived from the bacterial metabolism of dietary fibre, modulate CD8+ T-cell function and enhances the ability to dendritic cells to activate CD8+ T-cells. This work is being presented to the Society for Immunotherapy of Cancer annual meeting next month, prior to publication. We’re now using the data and experimental procedures developed in this project to study combinations of metabolites including the SCFA butyrate, calcitriol (vitamin D), Niacin (vitamin B3) and ‘low dose’ naltrexone (LDN). Our hypothesis is that combinations of these metabolites will correct T-cell dysfunction and ‘prime’ the T-cell to respond to cancer Immunotherapy. This hypothesis is informed both by our data and an in depth analysis of T-cell function in the setting of cancer which is due to be published as a review titled ‘Directing T-cell responses for cancer vaccination and Immunotherapy’ in the journal ‘Vaccines’ next month. 

A second review titled ‘The Diverse Effects of Phytochemicals and Dietary Supplementation on Cancer Immunotherapy’ is due to be published in the journal Immunology research. This review describes remarkable recent findings indicating that components of our diet, particularly those metabolised by our gut microbiome, are essential to the efficacy of cancer immunotherapy such as checkpoint inhibition and point towards the development of bespoke dietary advice to complement Immunotherapy treatment – the lack of such advice is currently a major impediment to the success of cancer immunotherapy. In support of this approach we are completing a systematic analysis of publicly available metabolite datasets, derived from clinical studies, in order to find patterns of metabolite expression that might otherwise be missed by the individual studies. Thus far our analysis has identified butyrate and Niacin (detailed above) alongside various phytochemicals. These phytochemicals include metabolites derived from the consumption of cashew nuts or soy.

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