PT  - JOURNAL ARTICLE
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
TI  - Antibiotic therapy and outcome from immune-checkpoint inhibitors
AID  - 10.1186/s40425-019-0775-x
DP  - 2019 Dec 01
TA  - Journal for ImmunoTherapy of Cancer
PG  - 287
VI  - 7
IP  - 1
4099  - http://jitc.bmj.com/content/7/1/287.short
4100  - http://jitc.bmj.com/content/7/1/287.full
SO  - J Immunother Cancer2019 Dec 01; 7
AB  - 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