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Review

Genomic and Epigenomic Biomarkers of Immune Checkpoint Immunotherapy Response in Melanoma: Current and Future Perspectives

by
Sultana Mehbuba Hossain
1,2,
Carien Carpenter
1 and
Michael R. Eccles
1,2,*
1
Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin 9016, New Zealand
2
Maurice Wilkins Centre for Molecular Biodiscovery, Level 2, 3A Symonds Street, Auckland 1010, New Zealand
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2024, 25(13), 7252; https://doi.org/10.3390/ijms25137252 (registering DOI)
Submission received: 12 May 2024 / Revised: 25 June 2024 / Accepted: 26 June 2024 / Published: 30 June 2024
(This article belongs to the Special Issue Melanoma: From Molecular Pathology to Therapeutic Approaches)

Abstract

Immune checkpoint inhibitors (ICIs) demonstrate durable responses, long-term survival benefits, and improved outcomes in cancer patients compared to chemotherapy. However, the majority of cancer patients do not respond to ICIs, and a high proportion of those patients who do respond to ICI therapy develop innate or acquired resistance to ICIs, limiting their clinical utility. The most studied predictive tissue biomarkers for ICI response are PD-L1 immunohistochemical expression, DNA mismatch repair deficiency, and tumour mutation burden, although these are weak predictors of ICI response. The identification of better predictive biomarkers remains an important goal to improve the identification of patients who would benefit from ICIs. Here, we review established and emerging biomarkers of ICI response, focusing on epigenomic and genomic alterations in cancer patients, which have the potential to help guide single-agent ICI immunotherapy or ICI immunotherapy in combination with other ICI immunotherapies or agents. We briefly review the current status of ICI response biomarkers, including investigational biomarkers, and we present insights into several emerging and promising epigenomic biomarker candidates, including current knowledge gaps in the context of ICI immunotherapy response in melanoma patients.
Keywords: melanoma; immunotherapy; PD-L1 expression; mutation burden; neoantigens; DNA methylation; m6A RNA methylation; long non-coding RNAs melanoma; immunotherapy; PD-L1 expression; mutation burden; neoantigens; DNA methylation; m6A RNA methylation; long non-coding RNAs

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MDPI and ACS Style

Hossain, S.M.; Carpenter, C.; Eccles, M.R. Genomic and Epigenomic Biomarkers of Immune Checkpoint Immunotherapy Response in Melanoma: Current and Future Perspectives. Int. J. Mol. Sci. 2024, 25, 7252. https://doi.org/10.3390/ijms25137252

AMA Style

Hossain SM, Carpenter C, Eccles MR. Genomic and Epigenomic Biomarkers of Immune Checkpoint Immunotherapy Response in Melanoma: Current and Future Perspectives. International Journal of Molecular Sciences. 2024; 25(13):7252. https://doi.org/10.3390/ijms25137252

Chicago/Turabian Style

Hossain, Sultana Mehbuba, Carien Carpenter, and Michael R. Eccles. 2024. "Genomic and Epigenomic Biomarkers of Immune Checkpoint Immunotherapy Response in Melanoma: Current and Future Perspectives" International Journal of Molecular Sciences 25, no. 13: 7252. https://doi.org/10.3390/ijms25137252

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