Accumulating evidence demonstrates the decisive role of the gut microbiota in determining the effectiveness of anticancer therapeutics such as immunogenic chemotherapy or immune checkpoint blockade in preclinical tumor models, as well as in cancer patients. In synthesis, it appears that a normal intestinal microbiota supports therapeutic anticancer responses, while a dysbiotic microbiota that lacks immunostimulatory bacteria or contains overabundant immunosuppressive species causes treatment failure. These findings have led to the design of clinical trials that evaluate the capacity of modulation of the gut microbiota to synergize with treatment and hence limit tumor progression. Along the lines of this Trial Watch, we discuss the rationale for harnessing the gut microbiome in support of cancer therapy and the progress of recent clinical trials testing this new therapeutic paradigm in cancer patients.

Candiolo Cancer Institute FPO IRCCS 100 60 Turin Italy

Center of Clinical Investigations in Biotherapies of Cancer 1428 Villejuif France

Centre de Recherche des Cordeliers Equipe labellisée par la Ligue contre le cancer Université de Paris Sorbonne Université Inserm U1138 Paris France

Centre De Recherche Du Centre Hospitalier De l'Université De Montréal Montréal Canada

Centre Hospitalier De l'Université De Montréal Montréal Canada

CRUK Cambridge Institute University of Cambridge Cambridge UK

Department CIBIO University of Trento Trento Italy

Department of Dermatology Universitätsklinikum Erlangen Friedrich Alexander University 91054 Erlangen Germany

Department of Microbiology Tumor and Cell Biology and Science for Life Laboratory Karolinska Institutet Sweden

Department of Research Fondazione IRCCS Istituto Nazionale dei Tumori via G Amadeo 42 20133 Milan Italy

Department of Tumor Immunology Radboud Institute for Molecular Life Sciences Radboud University Medical Center Nijmegen Netherlands

EverImmune Villejuif France

Faculty of Medicine Université Paris Saclay Le Kremlin Bicêtre France

Gustave Roussy Comprehensive Cancer Institute Villejuif France

HalioDx is a biotech company

IIGM Italian Institute for Genomic Medicine c o IRCCS Candiolo 10060 Candiolo Turin Italy

INSERM U1015 Villejuif France

Karolinska Institute Department of Women's and Children's Health Karolinska University Hospital Sweden

Medicine and Research GBG Forschungs GmbH Neu Isenburg Germany

Metabolomics and Cell Biology Platforms Institut Gustave Roussy Villejuif France

Pôle De Biologie Hôpital Européen Georges Pompidou AP HP Paris France

RECETOX Faculty of Science Masaryk University Brno Czech Republic

Suzhou Institute for Systems Medicine Chinese Academy of Medical Sciences Suzhou China

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