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Leading article
Microbiota and cancer immunotherapy: in search of microbial signals
  1. Raad Z Gharaibeh1,
  2. Christian Jobin1,2,3
  1. 1 Department of Medicine, University of Florida, Gainesville, Florida, USA
  2. 2 Department of Infectious Diseases and Immunology, University of Florida, Gainesville, Florida, USA
  3. 3 Department of Anatomy and Cell Biology, University of Florida, Gainesville, Florida, USA
  1. Correspondence to Dr Christian Jobin, Department of Medicine, University of Florida, Gainesville FL 32611, USA; Christian.Jobin{at}medicine.ufl.edu

https://doi.org/10.1136/gutjnl-2018-317220

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    The intestinal microbiota, a conglomerate of microorganisms comprising bacteria, viruses, archaea and fungi, has been recognised as an important component of host physiology through, for example, its influence on nutritional biotransformation, immune response and xenobiotic metabolism.1 These functions are performed via a complexed and multilayer set of controls coming from within the microbial community as well as host factors. Consequently, this intricate microbiota–host partnership is viewed as an essential element of health. For example, intestinal bacterial, fungal and viral composition is different in patients with IBDs and colorectal cancer compared with healthy subjects.2–4 A number of investigative lines probing the impact of microbiota in disease initiation, progression and therapeutics are currently underway. The microbial therapeutic field is particularly dynamic, in part due to the impressive success of faecal microbiota transplantation (FMT) for treatment of recurrent Clostridium difficile infection.5 Whether FMT or derivative synthetic cocktail could be applied to other disease conditions is unclear, and a number of clinical trials for the treatment of metabolic syndrome, diabetes and IBD are currently underway to address this question.

    The field of cancer has been particularly attentive to the interaction between bacteria and therapeutics.6 7 This impact of bacteria on therapeutics is wide and includes modulation of chemotherapeutic and immunotherapeutic agents’ efficacy and toxicity via metabolic and immune-mediated mechanisms.8–11 In particular, the recent discovery that intestinal microbiota profoundly impacts responses of patients with cancer to immune checkpoint blockade therapy (Routy et al,12 Gopalakrishnan et al 13 and Matson et al 14) has attracted much attention. In these studies, the authors used an antibody targeting the coinhibitory receptor/ligand system programmed death-1 (PD-1)/PDL-1 administered to patients with metastatic melanoma13 14 or non-small cell lung cancer and renal cell carcinoma.12 The overall hypothesis pursued by these research teams was …

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