Antibiotic therapy and outcome from immune-checkpoint inhibitors

J Immunother Cancer. 2019 Nov 6;7(1):287. doi: 10.1186/s40425-019-0775-x.

Abstract

Sensitivity to immune checkpoint inhibitor (ICPI) therapy is governed by a complex interplay of tumor and host-related determinants. Epidemiological studies have highlighted that exposure to antibiotic therapy influences the probability of response to ICPI and predict for shorter patient survival across malignancies. Whilst a number of studies have reproducibly documented the detrimental effect of broad-spectrum antibiotics, the immune-biologic mechanisms underlying the association with outcome are poorly understood. Perturbation of the gut microbiota, an increasingly well-characterized factor capable of influencing ICPI-mediated immune reconstitution, has been indicated as a putative mechanism to explain the adverse effects attributed to antibiotic exposure in the context of ICPI therapy. Prospective studies are required to validate antibiotic-mediated gut perturbations as a mechanism of ICPI refractoriness and guide the development of strategies to overcome this barrier to an effective delivery of anti-cancer immunotherapy.

Keywords: Antibiotics; Immune checkpoint inhibitors; Survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / therapeutic use
  • Antineoplastic Agents, Immunological / pharmacology
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Drug Interactions*
  • Host-Pathogen Interactions
  • Humans
  • Neoplasms / diagnosis
  • Neoplasms / drug therapy*
  • Neoplasms / mortality*
  • Prognosis
  • Treatment Outcome

Substances

  • Anti-Bacterial Agents
  • Antineoplastic Agents, Immunological