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DNA methylation-based prediction of response to immune checkpoint inhibition in metastatic melanoma

Filipski, Katharina, Scherer, Michael, Zeiner, Kim N, Bucher, Andreas, Kleemann, Johannes, Jurmeister, Philipp, Hartung, Tabea I, Meissner, Markus, Plate, Karl H, Fenton, Tim R., and others. (2021) DNA methylation-based prediction of response to immune checkpoint inhibition in metastatic melanoma. Journal for ImmunoTherapy of Cancer, 9 (7). E-ISSN 2051-1426. (doi:10.1136/jitc-2020-002226) (KAR id:89373)

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https://jitc.bmj.com/content/9/7/e002226

Abstract

Background Therapies based on targeting immune checkpoints have revolutionized the treatment of metastatic melanoma in recent years. Still, biomarkers predicting long-term therapy responses are lacking.

Methods A novel approach of reference-free deconvolution of large-scale DNA methylation data enabled us to develop a machine learning classifier based on CpG sites, specific for latent methylation components (LMC), that allowed for patient allocation to prognostic clusters. DNA methylation data were processed using reference-free analyses (MeDeCom) and reference-based computational tumor deconvolution (MethylCIBERSORT, LUMP).

Results We provide evidence that DNA methylation signatures of tumor tissue from cutaneous metastases are predictive for therapy response to immune checkpoint inhibition in patients with stage IV metastatic melanoma.

Conclusions These results demonstrate that LMC-based segregation of large-scale DNA methylation data is a promising tool for classifier development and treatment response estimation in cancer patients under targeted immunotherapy.

Item Type: Article
DOI/Identification number: 10.1136/jitc-2020-002226
Subjects: Q Science > QP Physiology (Living systems) > QP506 Molecular biology
R Medicine
Divisions: Divisions > Division of Natural Sciences > School of Biosciences
Depositing User: Tim Fenton
Date Deposited: 20 Jul 2021 08:27 UTC
Last Modified: 21 Jul 2021 08:23 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/89373 (The current URI for this page, for reference purposes)
Fenton, Tim R.: https://orcid.org/0000-0002-4737-8233
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