Immuno-Oncology & the Microbiome

The microbiome is receiving significant attention in regards to its influence on cancer. Its role in response to cancer treatment is becoming increasingly evident, with research showing that harnessing the gut microbiome may affect responses to numerous forms of cancer treatments. Several companies are now looking to develop microbiome-based complementing therapeutics as well as LBPs designed to potentially treat tumours. This session will look at understanding factors influencing the gut microbiome, strategies to augment therapeutic responses as well as engineering the microbiome for precision therapy.

The Role of the Microbiota in Regulating Breast Cancer

By: Stephen Robinson, Research Leader, Quadram Institute

Modulation of the gut microbiota has been shown to influence primary tumour growth across multiple diseases; however, despite breast cancer being so common in the Western World, there have been a paucity of studies addressing the role of the microbiome. We have shown that antibiotic induced dysbiosis accelerates primary tumour growth. However, to our surprise this appears to be largely driven by metabolic changes rather than immunological modulation. We have also shown that the microbiome plays a role in guiding and controlling metastatic breast cancer by influencing the metastatic niche. Overall, these findings have demonstrated a key role for the microbiome in breast cancer growth and progression. Our data suggests that antibiotic use in BC patients should be examined closely and re-evaluated to avoid comprising treatment efficacy.

Stephen started his scientific career studying mammary gland biology under the supervision of Professor Charles Daniel at the University of California, Santa Cruz. His work focused on understanding how TGF-beta isoforms regulate breast development, functional differentiation, and cancer. He then conducted my postdoctoral work at the Massachusetts Institute of Technology with Professor Richard Hynes. Here he developed Selectin double- and triple-knockout mice, and showed P-selectin plays a dominant role in leukocyte trafficking. In 2000, Stephen moved from to the United Kingdom to work with Professor Kairbaan Hodivala-Dilke at Barts Cancer Institute. They published ground that have changed the research community’s perception of how integrins function in vivo to regulate both normal and pathological angiogenesis. In 2011 he became an independent group leader at the University of East Anglia (UEA). His group has elucidated the endothelial specific function of αvβ3-integrin in angiogenesis, showing the molecule’s role in the process is context specific, particularly with respect to its regulation over angiogenic signalling pathways. In 2018, Stephen became a Research Leader at the Quadram Institute

to understand how microbiome-host interactions regulate health and disease, with major focuses on vascular development and homeostasis, and cancer.

Precision Therapy in Colorectal Cancer: Defining the Role of the Gut Microbiome

By James Kinross, Senior Lecturer and Consultant Colorectal Surgeon, Imperial College London

Sporadic colorectal cancer (CRC) remains the second leading cause of cancer deaths in the UK and it is a disease whose aetiology is defined primarily by interactions between the host and his environment. The gut microbiota, which sits at the interface between the host’s physiology and exposome, is now recognised as a critical modulator in CRC aetiology. However, our understanding of this immensely complex, highly individualised and multi-faceted relationship is incomplete. We have demonstrated that gut microbiota composition is indicative of CRC disease stage and molecular phenotype, and we have defined anti-correlated community sub-types, that defines this association. Utilising liquid-chromatography mass spectrometry we have analysed how metabolomic changes in the developing tumour micro-environment provide insight into the microbial driver and passenger co-metabolic functions that in turn influence cancer phenotypes and treatment response. Moreover, we have mapped how the gut microbiome influences chemotherapeutic efficacy and toxicity through the proposed TIMER framework. We now propose a novel model for future precision therapy in colorectal cancer and outline future opportunities for engineering the microbiome for improved patient outcomes.

James Kinross is a Senior Lecturer and conusultant colorectal surgen at Imperial College London. He was awarded his PhD in 2010 and has published extensively on the gut microbiome. His research group is studying how the gut microbiome initiates colorectal cancer and exploring how it may be engineered to improve patient outcomes from surgery and chemoradiotherapy.

Metagenomics for Evaluation of Chemotherapy Impact on Gut Microbiome

By Françoise Le Vacon, Chief Scientific Officer, Biofortis Mérieux NutriSciences

It is now well established that, besides genetic features, one major host determinant in human health is the gut microbiome. The French consortium IMODI (Innovative MODels Initiative) aims to develop predictive preclinical mouse models for new chemotherapeutic treatment discovery, to progress toward personalized medicine. In this consortium, Biofortis Mérieux NutriSciences issue is to better understand how the treatment can impact the gut microbiome of patients and of mouse models named Patient-Derived Tumor Xenograft (PDX). In this purpose, we coordinate a clinical study to recruit patients with four types of cancer (breast, ovary, liver and prostate) from french clinical centers. Stool samples from patients and PDX are collected and the gut microbiome composition is assessed by 16S rRNA gene sequencing before, during and after chemotherapy. The taxonomic classification of sequences is obtainedusing bioinformatics and statistics skills. Our work shows that some chemotherapeutic agents could have a specific effect on gut microbiome. Imodi stool and blood biobank is available for the scientific community. This study supports that the microbiome is an important additional parameter for evaluating the toxicity of pharmacological treatments. The evaluation of the microbiome in the development of new therapeutic agents is highly recommended.

Dr. Françoise Le Vacon is an expert in Molecular Biology. In 1996, she founded Atlangene Applications, which is now integrated within Biofortis. Françoise obtained a Master’s degree in Cellular and Molecular Biology from the University of Rennes, France, in 1985. She then obtained a PhD from the Faculty of Sciences at the University of Nantes, France, having carried out work of key importance at the INSERM U211 laboratory under Prof. Francine Jotereau, on the subject of “Murin’s Lymphomas induced by Abelson Virus” in 1990. Following various assignments at the Hôpital Cochin and Institut Pasteur in Paris, and the Johns Hopkins Hospital and National Institute of Health in the U.S., she has held research and development managerial positions for the last 20 years. She has also worked as a researcher at the René Gauducheau Centre for Cancer Care in Nantes, and as a laboratory manager at the Grenoble Transfusion Center. She joined Silliker France in 2007 as the Molecular Biology Laboratory Manager in Food Quality and Safety, with expertise in food allergens. As Microbiota Research Program Director at Biofortis, Françoise set up a platform for the study of bacterial ecosystems for nutrition and health. In 2011, Françoise received the French National Order of Merit for her contribution to science.

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