The interplay between gut microbiota, antibiotics, and immune checkpoint inhibitors in patients with cancer: A narrative review with biological and clinical aspects

Abstract

Immune checkpoint inhibitors (ICIs) targeting the programmed cell death-1 (PD-1), programmed cell death ligand-1 (PD-L1), and cytotoxic T-lymphocyte antigen 4 (CTLA-4) pathways have revolutionized cancer therapy. However, primary and secondary resistance to ICI pose significant challenges. Recent studies underscore the critical role of gut microbiota (GM) in modulating ICI efficacy by shaping host immune responses and regulating the tumor microenvironment (TME). The composition of the GM has been linked to ICI treatment outcomes, with certain microbial taxa, such as Faecalibacterium spp., Bifidobacterium spp., Eubacterium spp., Roseburia spp., and Akkermansia muciniphila, associated with favorable responses. Mechanistically, the GM affects immune responses via multiple pathways, including induction of T cell differentiation, promotion of anti- or proinflammatory cytokine environments, and enhancement of T cell priming and effector functions. Moreover, microbial-derived metabolites play a role in shaping tumor immune responses and influencing ICI efficacy. Antibiotic treatment can disrupt GM diversity and composition (gut dysbiosis), potentially diminishing ICI effectiveness. A deeper understanding of the interplay between GM, antibiotic treatment, and ICI efficacy is crucial for developing personalized therapeutic strategies to improve patient outcomes. Herein, we review current evidence on the association between specific microbial taxa and tumor immunosurveillance, the impact of antibiotics on the GM composition and immune modulation, and its implications for ICI therapy efficacy.

Keywords: Antibiotics; Clinical outcome; Immune checkpoint inhibitors; Immune response; Microbiota; dysbiosis.