Abstract

Cancer immunotherapy has transformed oncology, yet clinical outcomes remain highly variable among patients. 
Emerging evidence highlights the microbiome as a critical determinant of therapeutic efficacy and toxicity. 
Microbial communities influence tumor progression, immune surveillance, and the effectiveness of treatments such 
as immune checkpoint inhibitors (ICIs) and chimeric antigen receptor (CAR) T-cell therapy. Specific microbiome 
signatures characterized by enhanced diversity, enrichment of commensal taxa, and metabolite-mediated 
immunomodulation correlate with improved responses, whereas dysbiosis and reduced diversity are linked to 
resistance and adverse events. Immunotherapy itself also reshapes microbial ecosystems, underscoring a 
bidirectional relationship. Strategies to modulate the microbiome, including probiotics, prebiotics, dietary 
interventions, and fecal microbiota transplantation (FMT), have shown promise in preclinical and early clinical 
studies, with several trials demonstrating improved outcomes in refractory cancers. Despite encouraging findings, 
challenges remain, including methodological variability, reproducibility, and ethical considerations regarding 
microbiome interventions. Advances in metagenomics, multi-omics integration, and machine learning are 
accelerating the identification of predictive microbiome biomarkers, opening opportunities for microbiome-guided 
patient stratification and personalized immunotherapy. Harnessing microbiome signatures could thus optimize 
cancer treatment, reduce toxicity, and enable a new era of precision oncology. 
Keywords: Cancer immunotherapy, Microbiome signatures, Immune checkpoint inhibitors, CAR T-cell therapy, 
and fecal microbiota transplantation.