Harnessing the Gut Microbiome in Cancer Immunotherapy: Mechanisms, Challenges, and Routes to Personalized Medicine-A Systematic Review.

IntroductionImmunotherapy approaches have improved by Immune check point inhibitors such as PD-1, CTLA-4, and PD-L1 inhibitors. However, the response to immunotherapy varies widely among patients due to various factors. Co-administration of probiotics with ICIs has become a promising strategy to improve therapeutic outcomes. This review evaluates the impact of environmental factors and life style on cancer pathophysiology, outcome of disease, and response to the treatment. It evaluates the role of probiotics in modulating immune responses and the synergistic interaction of probiotics with immunotherapy.MethodsWe conducted a comprehensive systematic review of clinical and preclinical studies to assess the effects of probiotics on immunotherapy outcomes. Studies were selected based on their focus on probiotics' role in immune response modulation and interaction with ICIs. Data from trials involving patients with varying responses to immunotherapy, including those with prior resistance, were analyzed to explore the probiotic-enhanced immunotherapy.ResultsGut microbiome has wide effects on immune responses through different pathways like production of short chain fatty acids (SCFAs), polysaccharide A, and indole-3-carbaldehyde. Also, probiotics found to enhance Anit-inflammatory responses and increase CD8+ T-cell activity, suggesting a synergistic effect with ICIs. Gut microbiota composition plays a key role in determining the effectiveness of immunotherapy, especially in treatment-resistant patients. For optimized treatment outcomes, personalized probiotics tailored to individual's microbiota showed potential. Important challenges are treatment resistance and compromised mucosal integrity because of microbiome alterations. Effective drug delivery also remains as important barriers to common adoption.ConclusionFor immunotherapy outcomes improvement, immune responses modulation and gut microbiome diversity enhancement show probiotics important promise. Despite their potential, limitations must be addressed including treatment resistance and also delivery challenges. In order to maximize therapeutic benefits, personalized probiotic strategies have to be developed, and also the mechanisms by which probiotics improve ICI efficacy require elucidation through further research.