Systematic Reviews
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Nov 24, 2022; 13(11): 929-942
Published online Nov 24, 2022. doi: 10.5306/wjco.v13.i11.929
Gut microbiota diversity and composition in predicting immunotherapy response and immunotherapy-related colitis in melanoma patients: A systematic review
Oliver Oey, Yu-Yang Liu, Angela Felicia Sunjaya, Daniel Martin Simadibrata, Muhammad Adnan Khattak, Elin Gray
Oliver Oey, Department of Medical Oncology, St John of God Midland Public and Private Hospital, Midland, Perth 6004, WA, Australia
Oliver Oey, School of Medicine, University of Western Australia, Perth 6009, WA, Australia
Yu-Yang Liu, School of Medicine, University of Queensland, Brisbane 4072, QLD, Australia
Angela Felicia Sunjaya, Faculty of Medicine, Tarumanagara University, Jakarta 11440, Indonesia
Daniel Martin Simadibrata, School of Medicine, University of Indonesia, Jakarta 10430, Indonesia
Muhammad Adnan Khattak, Department of Medical Oncology, Fiona Stanley Hospital, Perth 6150, WA, Australia
Muhammad Adnan Khattak, Elin Gray, School of Medical Sciences, Edith Cowan University, Perth 6027, WA, Australia
Muhammad Adnan Khattak, Elin Gray, Centre for Precision Health, Edith Cowan University, Perth 6027, WA, Australia
Author contributions: Oey O, Simadibrata DM, Gray E and Khattak MA contributed to the study conception and design; Oey O and Liu Y performed data extraction; Oey O and Simadibrata DM performed risk of bias assessment; Oey O, Liu Y, Sunjaya AF, Simadibrata DM, Khattak MA and Gray E performed data analysis; Oey O written the first draft of the manuscript; all authors commented on previous versions of the manuscript, read and approved the final manuscript.
Conflict-of-interest statement: Khattak MA reports receiving travel support from Merck Sharp and Dohme (MSD), Bristol-Myers Squibb and Merck Serono. Gray E reports receiving travel sponsorship from MSD. Oey O, Liu Y, Sunjaya AF, and Simadibrata DM report no competing interests.
PRISMA 2009 Checklist statement: All authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Oliver Oey, MD, Doctor, Researcher, Department of Internal Medicine, St John of God Midland Public and Private Hospital, Midland, No. 1 Clayton Street, Perth 6004, WA, Australia.
Received: October 19, 2022
Peer-review started: October 19, 2022
First decision: October 28, 2022
Revised: October 30, 2022
Accepted: November 6, 2022
Article in press: November 6, 2022
Published online: November 24, 2022
Research background

Survival for metastatic melanoma has significantly improved since the introduction of immune checkpoint blockade (ICB) therapy. However, despite their considerable efficacy, 40%-60% of melanoma patients do not experience objective responses to the therapy. Additionally, some patients experience ICB-related colitis as a consequence of ICB therapy, preventing them from deriving the full benefit of ICB therapy. Recent studies have demonstrated that the gut microbiome (GM) may affect tumor immunity by regulating the host immune system and tumor micro-environment, thus suggesting that GM may affect response to ICB therapy and susceptibility of ICB-related colitis.

Research motivation

The GM has shown great potential as a biomarker of response to ICB therapy in melanoma patients. Previous studies investigating GM composition and/or diversity in patients with melanoma have identified distinct GM composition and diversity in responders to ICB compared to non-responders, as well as those more susceptible to ICB-related colitis than those who are not.

Research objectives

To be the first to compile the existing data regarding the role of GM composition and diversity in predicting response to ICB and ICB-related colitis specifically in patients with melanoma.

Research methods

Comprehensive literature search was done in various platforms using the following search terms: (fecal OR gut) AND (microbiota OR microbiome) AND (melanoma) AND (immunotherapy OR checkpoint OR nivolumab OR ipilimumab OR pembrolizumab). From a total of 300 studies, nine studies met inclusion criteria. Two studies were phase I clinical trials, while the remainder were prospective observational studies. All but one study has moderate risk of bias. Data from these studies including but not limited to, number of participants, type of immunotherapy received, GM analysis method, and GM composition and diversity were collected and interpreted.

Research results

Fecal samples enriched in Firmicutes phylum were associated with good response to ICB therapy, however they were associated with increased susceptibility to ICB-related colitis. Fecal samples enriched in Bacteroidales family were associated with poor response to ICB. Samples with greater GM diversity were associated with more favorable response to ICB. Fecal samples enriched in Bacteroidetes were associated with decreased incidence of ICB-related colitis. Overall, there was limited concordance in the organisms in the GM identified to be associated with response to ICB, and studies evaluating GM diversity showed conflicting results.

Research conclusions

GM composition and diversity holds some potential as a biomarker of response and toxicity to ICB in melanoma. Further prospective studies, including several RCTs that are underway, are needed to confirm whether the GM could be used as a biomarker and potential intervention to modulate ICB response in melanoma patients.

Research perspectives

With other promising biomarkers, GM composition and diversity holds potential to be integrated into a multiparameter model to accurately predict which subset of melanoma patients are likely to respond to ICB.