TY - JOUR T1 - Antibiotic therapy and outcome from immune-checkpoint inhibitors JF - Journal for ImmunoTherapy of Cancer JO - J Immunother Cancer DO - 10.1186/s40425-019-0775-x VL - 7 IS - 1 SP - 287 AU - David J. Pinato AU - Daria Gramenitskaya AU - Daniel M. Altmann AU - Rosemary J. Boyton AU - Benjamin H. Mullish AU - Julian R. Marchesi AU - Mark Bower Y1 - 2019/12/01 UR - http://jitc.bmj.com/content/7/1/287.abstract N2 - 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.Abbreviations:ATBAntibioticcATBConcurrent antibiotic treatmentCDCluster of DifferentiationCTLA-4Cyotoxic T-Lymphocyte Associated Protein 4DCRDisease control rateEIOPEarly Immunotherapy PeriodGIGastrointestinalHRHazard RatioICPIImmune-checkpoint inhibitorsLPSLipopolysaccharideMHCMajor Histocompatibility ComplexNOD1Nucleotide-binding oligomerization domain-containing protein 1NSCLCNon-small Cell Lung CancerORROverall response rateOSOverall SurvivalpATBPrior antibiotic treatmentPDProgressive DiseasePD-1Programmed Cell-Death 1PD-L1Programmed Cell-Death Ligand 1PFSProgression-free survivalRCCRenal Cell CarcinomaRRResponse rateTHT-Helper cellTLRToll-like receptorsWIOPWhole immunotherapy Period ER -