Collectively known as the microbiota, the commensal bacteria and other microorganisms that colonize the epithelial surfaces of our body have been shown to produce small molecules and metabolites that have both local and systemic effects on cancer onset, progression and therapy response. To date, most studies focusing on the microbiome have used traditional preclinical mouse models and identified correlative relationships between microbial species and cancer phenotypes. Now, the profound influence of the microbiota on the efficacy of cancer treatments, such as immunotherapies, has begun to be extensively characterized in humans. Paramount to the development of microbiota-based therapeutics, the next challenge in microbiome research will be to identify individual microbial species that causally affect cancer phenotypes and unravel the underlying mechanisms. In this Viewpoint article, we asked four scientists working on the cancer microbiome for their opinions on the current state of the field, where the research is heading and how we can advance our understanding to rationally design microbial-based therapeutics to transform treatment strategies for patients with cancer.
Eran Elinav is a professor in the Immunology Department, Weizmann Institute of Science, Israel, and the Director of the Cancer-Microbiome Division, Deutsches Krebsforschungszentrum (DKFZ), Germany. His research focuses on deciphering the molecular basis of host–microbiome interactions and their effects on health and disease, with a goal of personalizing medicine and nutrition.
Wendy S. Garrett is a professor of immunology and infectious diseases at Harvard and a medical oncologist in the Gastrointestinal Cancer Center at Dana-Farber Cancer Institute. She is co-director of the Harvard Chan Center for the Microbiome in Public Health. Her laboratory seeks to carry out mechanistic microbiome studies focused on cancer, inflammatory bowel disease and immune and epithelial cell development and function.
Giorgio Trinchieri is a US National Institutes of Health (NIH) Distinguished Investigator and Director of the Cancer and Inflammation Program, Center for Cancer Research (CCR), National Cancer Institute (NCI), NIH. His research has focused for many years on the interplay between inflammation, innate resistance and adaptive immunity and on the role of pro-inflammatory cytokines and interferons in the regulation of haematopoiesis, innate resistance and immunity against infections and tumours. The present focus of his laboratory is on the role of inflammation, innate resistance, immunity and the commensal microbiota in carcinogenesis, cancer progression and prevention or therapy of cancer.
Jennifer Wargo is an Associate Professor of Surgical Oncology and Genomic Medicine at the University of Texas MD Anderson Cancer Center and is a co-leader of the Melanoma Moon Shot programme. Her primary interests are in response and resistance to targeted therapy for melanoma and other cancers, neoadjuvant strategies and the influence of the gut and tumour microbiome on immunity and antitumour immune responses.
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E.E. thanks all the students, postdocs and employees at the Elinav laboratory at Weizmann Institute of Science and Deutsches Krebsforschungszentrum (DKFZ) for their continued partnership. E.E. is a senior fellow of the Canadian Institute of Advanced Research (CIFAR) and an international scholar of the Bill and Melinda Gates Foundation and Howard Hughes Medical Institute (HHMI). W.S.G. thanks members of her laboratory and collaborators for stimulating discussions as well as the US National Institutes of Health (NIH) National Cancer Institute (NCI) and Cancer Research UK for research support. J.W. thanks the patients who contributed to these studies, as well as the faculty, staff, students and postdoctoral fellows at the University of Texas MD Anderson Cancer Center who contributed to this work (which was supported by the Melanoma Moon Shot programme). J.W. also thanks worldwide collaborators for providing critical insight and opportunities to learn together. J.W. is a member investigator of the Parker Institute for Cancer Immunotherapy and is also an awardee of an Innovative Research Grant from Stand Up to Cancer–American Association for Cancer Research. J.W.’s research efforts are also supported by a Sabin Family Fellowship, the Melanoma Research Alliance and the NIH (1R011CA219896-01A1).
E.E. is a paid consultant at DayTwo and BiomX. E.E. states that none of the issues covered in this piece are related to, funded or endorsed by, shared or discussed with or licensed to these commercial entities. W.S.G. is a member of the scientific advisory boards for Evelo Biosciences, Kintai Therapeutics and Leap Therapeutics. G.T. declares no competing financial interests. J.W. is an advisory board member and consultant and adviser for AstraZeneca, Bristol-Myers Squibb, F. Hoffman–La Roche–Genentech, GlaxoSmithKline, Merck Sharp & Dohme, MicrobiomeDX, Biothera Pharmaceuticals and Novartis Pharmaceuticals Corporation, receives grant, clinical and research support from Bristol-Myers Squibb, F. Hoffman–La Roche–Genentech, GlaxoSmithKline and Novartis Pharmaceuticals Corporation, is a speakers bureau participant with Bristol-Myers Squibb, Dava Oncology, Gilead Sciences, Illumina, Imedex, MedImmune and Omniprex and receives other financial or material support from a US patent application (PCT/US17/53.717) submitted by the University of Texas MD Anderson Cancer Center that covers methods to enhance immune checkpoint blockade responses by modulating the microbiome.
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