Review Article: Fecal Microbiota Transplantation in Melanoma: Mechanisms-Mediated Enhancement of Anti-Tumor Immunotherapy

Jun 25, 2025Critical reviews in oncogenesis

How Fecal Microbiota Transplants May Improve Immunotherapy for Melanoma

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Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

Fecal microbiota transplantation (FMT) may enhance treatment efficacy in melanoma patients resistant to immune checkpoint inhibitors.

The gut microbiota influences health by affecting nutrition, metabolism, and immunity.
Dysbiosis is associated with cancer development and treatment resistance.
Melanoma accounts for over 80% of skin cancer-related deaths despite being only 1% of skin cancer cases.
Immune checkpoint inhibitors have improved survival in melanoma patients, but many do not achieve long-term responses.
FMT has potential to restore microbial balance and improve anti-tumor immunity.
Challenges remain regarding the safety of FMT, donor selection, and regulatory issues.

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The gut microbiota is integral to human health, influencing nutrition, metabolism, and immunity. Dysbiosis has been implicated in cancer development and resistance to therapies, highlighting the potential of microbiota modulation as a therapeutic strategy. Melanoma, while comprising only 1% of skin cancer diagnoses, accounts for over 80% of skin cancer related deaths, emphasizing the need for innovative approaches to enhance treatment efficacy. Although immune checkpoint inhibitors (ICIs) such as anti-programmed cell death protein (PD-1) and cytotoxic T-lymphocyte associated protein 4 (CTLA-4) blockade therapies have significantly improved survival for some melanoma patients, the majority fails to achieve durable responses and often develops long-term resistance to these treatments. Fecal microbiota transplantation (FMT) is emerging as a promising intervention to restore microbial balance and enhance treatment efficacy. This review explores the historical evolution and current applications of FMT in oncology, with a focus on its ability to modulate the gut microbiome, augment antitumor immunity, and overcome resistance to checkpoint blockade therapy in melanoma. Despite its promise, significant challenges remain, including ensuring the safety of the procedure, selecting suitable donors, and addressing regulatory hurdles. Future research aimed at optimizing FMT protocols, identifying key microbial strains, and understanding the mechanisms underlying microbiota-immune interactions will be essential to fully harness the potential of FMT as a transformative adjunct in cancer treatment.

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Review Article: Fecal Microbiota Transplantation in Melanoma: Mechanisms-Mediated Enhancement of Anti-Tumor Immunotherapy

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