• The Impact of Gut Microbiome Dysbiosis on Response to Immunotherapy in Melanoma Cancer Patients
  • Parisa Kalantari,1,* Soraya kalantari,2
    1. Department of paramedical, Faculty of Medical Sciences, Islamic Azad University, Arak, Iran
    2. Department of Medical ,Factually of Medicine, Yazd Medical Sciences , Islamic Azad University ,Yazd ,Iran


  • Introduction: Recent advances in cancer treatment have highlighted the crucial role of the immune system in combating malignancies. Immunotherapy has emerged as a promising approach, particularly in the treatment of melanoma, a highly aggressive form of skin cancer. However, patient responses to immunotherapy vary significantly, and understanding the factors that influence these responses is critical. Emerging evidence suggests that the gut microbiome, a complex community of microorganisms residing in the gastrointestinal tract, plays a pivotal role in modulating the immune system. Dysbiosis, or an imbalance in the gut microbiome, may influence the efficacy of immunotherapy. This study investigates the impact of gut microbiome dysbiosis on the response to immunotherapy in melanoma patients.
  • Methods: A total of 120 melanoma patients undergoing immunotherapy were recruited for this study. The sample comprised 70 males and 50 females, with a mean age of 55.2 years (range 30-75 years). Patients were selected based on the following inclusion criteria: confirmed diagnosis of melanoma, no prior history of gastrointestinal disorders, and no antibiotic use within six months prior to the study. Fecal samples were collected from all participants before the initiation of immunotherapy. Microbiome analysis was conducted using 16S ribosomal RNA gene sequencing to identify bacterial composition and assess the presence of dysbiosis. Patients were monitored over a six-month period to evaluate their response to immunotherapy. Clinical responses were categorized into complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) according to RECIST (Response Evaluation Criteria in Solid Tumors) guidelines. Statistical analyses were performed to correlate microbiome profiles with treatment outcomes.
  • Results: Microbiome analysis revealed significant variations in bacterial composition among patients. Notably, patients with higher abundance of Bacteroides and Faecalibacterium exhibited more favorable responses to immunotherapy. Specifically, 30 out of 120 patients (25%) achieved complete response (CR), with a mean abundance of Bacteroides at 14,000 sequences per sample and Faecalibacterium at 10,500 sequences per sample. Partial response (PR) was observed in 40 patients (33.3%), with mean Bacteroides and Faecalibacterium abundances of 11,500 and 8,000 sequences per sample, respectively. In contrast, patients with lower levels of these beneficial bacteria and higher levels of potentially pathogenic bacteria such as Clostridium and Escherichia showed poorer outcomes. Progressive disease (PD) was noted in 35 patients (29.2%), where mean Bacteroides and Faecalibacterium abundances were significantly lower at 5,000 and 4,000 sequences per sample, respectively. Stable disease (SD) was observed in 15 patients (12.5%), with intermediate bacterial abundances. Furthermore, the overall diversity of the gut microbiome, measured by the Shannon diversity index, was higher in responders (CR and PR) compared to non-responders (SD and PD). Responders had a mean Shannon diversity index of 4.5, whereas non-responders had a mean index of 3.2.
  • Conclusion: This study underscores the significant impact of gut microbiome composition on the efficacy of immunotherapy in melanoma patients. The presence of beneficial bacteria such as Bacteroides and Faecalibacterium appears to enhance treatment response, while dysbiosis characterized by low microbial diversity and high levels of pathogenic bacteria correlates with poorer outcomes. These findings suggest that modulating the gut microbiome through dietary interventions, probiotics, or fecal microbiota transplantation could potentially improve immunotherapy responses in melanoma patients. Further research is warranted to explore these therapeutic strategies and their implications in clinical practice.
  • Keywords: Gut microbiome, Dysbiosis, Immunotherapy, Melanoma, Cancer, Bacteroides, Faecalibacterium, Microbial