TY  - JOUR
A1  - Filipski, Katharina Johanna
A1  - Scherer, Michael
A1  - Zeiner, Kim Nikola
A1  - Bucher, Andreas
A1  - Kleemann, Johannes
A1  - Jurmeister, Philipp
A1  - Hartung, Tabea Isabelle
A1  - Meissner, Markus
A1  - Plate, Karl
A1  - Fenton, Tim R.
A1  - Walter, Jörn
A1  - Tierling, Sascha
A1  - Schilling, Bastian
A1  - Zeiner, Pia Susan
A1  - Harter, Patrick Nikolaus
T1  - DNA methylation-based prediction of response to immune checkpoint inhibition in metastatic melanoma
T2  - Journal for ImmunoTherapy of Cancer
N2  - 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.
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/64427
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-644275
SN  - 2051-1426
N1  - KF has received intramural funding by the Frankfurt Research Funding (FFF) program "Nachwuchswissenschaftler" and the "Clinician Scientist Program" by the Mildred-Scheel Foundation. MS is supported by the BMBF project de.NBI-epi (031L0101D) and the EU H2020 project SYSCID (733100). PSZ has received intramural funding by the FFF program "Nachwuchswissenschaftler" and "Patenschaftsprogramm" as well as within the "Clinician Scientist Program" by the Mildred-Scheel Foundation. The Dr Senckenberg Institute of Neurooncology is supported by the Dr Senckenberg Foundation. For this study, PNH obtained grants from “FCI/LOEWE: Discovery and Development Program”.
VL  - 9
IS  - e002226
SP  - 1
EP  - 11
PB  - BioMed Central
CY  - London
ER  -