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INTERNATIONAL CONGRESS OF

CancerGenetics

• Investigating the Role of the Gut Microbiome in the Response to Melanoma Immunotherapy

• Vajihe Ghalenoei,¹ Vahideh Hejininezhad,² Mahsa Karimzadeh ,³ Parvin Babaei ,^4,*
  1. BSc in Nursing, Faculty of Medical Sciences, Islamic Azad University of Birjand, South Khorasan, Iran
  2. Student Research Committee, School of Nursing and Midwifery, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
  3. Student Research Committee, School of Nursing and Midwifery, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
  4. MSc Pediatric Nursing Student, Student Research Committee, School of Nursing and Midwifery, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
  
  
  
• Introduction: Melanoma is a highly aggressive skin cancer that, in its advanced stages, is associated with an extremely poor prognosis. The advent of immunotherapies, particularly PD-1 inhibitors, has revolutionized the treatment landscape for this disease, leading to remarkable and durable clinical responses. Nevertheless, a significant number of patients fail to achieve a lasting response, often developing drug resistance and experiencing severe, immune-related adverse events. These clinical challenges underscore the urgent need to identify reliable biomarkers that can predict treatment efficacy and guide patient selection. An emerging and critical area of research in this context is the role of the gut microbiome. Growing evidence demonstrates that specific compositions of the gut microbiota may impact patients' response to immunotherapy, including both treatment efficacy and the development of adverse reactions. Therefore, investigation into the intricate relationship between the gut microbiome and the response to immunotherapy is crucial for deepening our understanding of melanoma and paving the way for the development of novel, microbiome-based therapeutic strategies.
• Methods: In this narrative review, an advanced literature search was conducted using a combination of Medical Subject Headings (MeSH) and non-MeSH terms, with Boolean operators. We searched for Persian and English articles using the keywords "gut microbiome," "immune checkpoint inhibitors," "melanoma," and "treatment response," in the following databases: PubMed, Scopus, Web of Science, and Google Scholar search engine, as well as national databases (SID and Magiran). The initial search yielded 66 articles. Based on our inclusion criteria (full-text articles published in Persian or English, between 2020–2025, with open access) and exclusion criteria (grey literature, letters, and comments), 34 studies were ultimately included for analysis, after removing duplicates and screening for relevance.
• Results: Research has established a significant association between the composition and diversity of the gut microbiome and the response to anti-PD-1 immunotherapy in melanoma patients. The data indicate that beneficial gut microbiota in responders enhance the activation and expression of CD cells, promoting robust T-cell activation. Conversely, non-responders presented with a less favorable gut microbiota composition and a higher frequency of regulatory T cells (Tregs). The association between the gut microbiome and immunotherapy responsiveness was first demonstrated in preclinical animal studies. In mouse models, the efficacy of anti-CTLA-4 therapy was directly influenced by gut microbial composition. The presence of specific commensal gut microbes, such as Bacteroides fragilis, Bacteroides thetaiotaomicron, Burkholderiales, and Bifidobacterium, was associated with enhanced tumor control. These findings were corroborated in human cohorts, where responders (Rs) and non-responders (NRs) to immunotherapy exhibited distinct gut microbiome profiles. For anti-PD-1 therapy, fecal samples from Rs showed greater bacterial diversity and a higher abundance of specific microbes, such as Clostridiales, Ruminococcaceae, and Faecalibacterium, compared to NRs. Furthermore, one study by Chaput et al. found that melanoma patients colonized with specific bacterial species had significantly longer progression-free survival on ICIs but also a much higher incidence of immune-mediated colitis (IMC).
• Conclusion: Recent findings highlight the important role of the gut microbiome as a potential indicator of how well patients respond to PD-1/PD-L1 immune checkpoint inhibitors in melanoma. The microbiome affects not only treatment effectiveness but may also contribute to the development of immune-related side effects. Therefore, altering the gut microbiome through methods such as probiotics, prebiotics, dietary changes, or fecal microbiota transplantation (FMT) has emerged as a promising strategy to improve treatment outcomes and overcome therapeutic resistance. Given the clinical significance of these findings, well-designed prospective studies and large clinical trials are needed to confirm these relationships and clarify the underlying biological processes. Ultimately, combining insights from the microbiome with other biomarkers may advance precision medicine and lead to tailored treatment strategies for melanoma patients.
• Keywords: Gut Microbiome, Immune Checkpoint Inhibitors, Melanoma, Treatment Response