The Microbiome in Advanced Melanoma: Where Are We Now?

Abstract

Purpose of review: This review summarizes recent data linking gut microbiota composition to ICI outcomes and gut microbiota-specific interventional clinical trials in melanoma.

Recent findings: Preclinical and clinical studies have demonstrated the effects of the gut microbiome modulation upon ICI response in advanced melanoma, with growing evidence supporting the ability of the gut microbiome to restore or improve ICI response in advanced melanoma through dietary fiber, probiotics, and FMT. Immune checkpoint inhibitors (ICI) targeting the PD-1, CTLA-4, and LAG-3 negative regulatory checkpoints have transformed the management of melanoma. ICIs are FDA-approved in advanced metastatic disease, stage III resected melanoma, and high-risk stage II melanoma and are being investigated more recently in the management of high-risk resectable melanoma in the peri-operative setting. The gut microbiome has emerged as an important tumor-extrinsic modulator of both response and immune-related adverse event (irAE) development in ICI-treated cancer in general, and melanoma in particular.

Keywords: Cytotoxic T-lymphocyte antigen-4 (CTLA-4); Gut microbiome; Immunotherapy; Melanoma; Programmed death-1 (PD-1).

Figure 1.

Factors affecting gut microbiome composition

Figure 2.

Microbiome interventions in cancer treatment