Immune Checkpoint Inhibitor Therapy for Metastatic Melanoma: What Should We Focus on to Improve the Clinical Outcomes?

Int J Mol Sci. 2024 Sep 20;25(18):10120. doi: 10.3390/ijms251810120.

Abstract

Immune checkpoint inhibitors (ICIs) have transformed cancer treatment by enhancing anti-tumour immune responses, demonstrating significant efficacy in various malignancies, including melanoma. However, over 50% of patients experience limited or no response to ICI therapy. Resistance to ICIs is influenced by a complex interplay of tumour intrinsic and extrinsic factors. This review summarizes current ICIs for melanoma and the factors involved in resistance to the treatment. We also discuss emerging evidence that the microbiota can impact ICI treatment outcomes by modulating tumour biology and anti-tumour immune function. Furthermore, microbiota profiles may offer a non-invasive method for predicting ICI response. Therefore, future research into microbiota manipulation could provide cost-effective strategies to enhance ICI efficacy and improve outcomes for melanoma patients.

Keywords: ICI; anti-tumour immune response; epigenetic regulation; melanoma; microbiota; predicting treatment outcomes; treatment resistance.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Immune Checkpoint Inhibitors* / pharmacology
  • Immune Checkpoint Inhibitors* / therapeutic use
  • Immunotherapy / methods
  • Melanoma* / drug therapy
  • Melanoma* / immunology
  • Melanoma* / pathology
  • Microbiota / drug effects
  • Neoplasm Metastasis
  • Treatment Outcome

Substances

  • Immune Checkpoint Inhibitors

Grants and funding

This research was funded by Otago Medical Research Foundation (AG-400). S.M.H. is supported by a Postdoctoral Fellowship from the New Zealand Institute for Cancer Research Trust. Kevin Ly is supported by New Zealand Cancer Society Postdoctoral Fellowship. A. Braithwaite is supported by New Zealand HRC programme grant (23/470). Y.J. Sung and Kunyu Li are supported by New Zealand HRC project grant (23/301).