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Background: Immune checkpoint inhibitors have transformed cancer treatment, yet only a subset of patients achieve durable clinical benefit. Increasing evidence indicates that the intestinal microbiota plays a key role in regulating antitumor immune responses. Antibiotic therapy, by disrupting microbial homeostasis, may negatively influence the effectiveness of immunotherapy. Objectives: This narrative review aims to synthesize current preclinical and clinical evidence regarding the impact of antibiotic exposure on the efficacy of immune checkpoint inhibitor therapy, with particular attention to timing of exposure, tumor type, and underlying biological mechanisms. Methods: A focused literature search was conducted using major biomedical databases to identify relevant preclinical studies, retrospective and prospective clinical cohorts, and systematic reviews examining the relationship between antibiotic use and immunotherapy outcomes. Due to heterogeneity in study design and exposure definitions, findings were analyzed narratively. Results: Across multiple tumor types, antibiotic exposure was consistently associated with inferior clinical outcomes, including reduced progression-free survival, overall survival, and treatment response. The negative association was most pronounced when antibiotics were administered shortly before initiation of immunotherapy. Meta-analyses confirmed the robustness of this signal despite substantial heterogeneity and methodological limitations. Emerging translational and early interventional studies suggest that modulation of the gut microbiome may partially restore immunotherapy responsiveness. Conclusions: Current evidence supports a clinically relevant association between antibiotic exposure and reduced immunotherapy efficacy. While causality cannot be definitively established, these findings highlight the importance of judicious antibiotic use in patients receiving immunotherapy and underscore the need for prospective, microbiome-integrated studies to guide future clinical practice.
Zdobylak et al. (Fri,) studied this question.