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Genome-wide DNA methylation profile analysis identifies an individualized predictive signature for melanoma immune response.
- Source :
-
Journal of Cancer Research & Clinical Oncology . Jan2023, Vol. 149 Issue 1, p343-356. 14p. - Publication Year :
- 2023
-
Abstract
- Purpose: The current evaluation methods for tumor infiltrating lymphocytes (TILs), particularly CD8 + TILs, mainly rely on semiquantitative immunohistochemistry with high variability. We aimed to construct an individualized DNA methylation-based signature for CD8 + TILs (CD8 + MeTIL) that may characterize melanoma immune microenvironment and guide therapeutic selection. Methods: The transcriptome profiles and DNA methylation data of 457 melanoma patients from The Cancer Genome Atlas (TCGA) database were analyzed. Differential methylation analysis between groups with high and low CD8 + TILs was performed to select differentially methylated positions (DMPs) and define CD8 + MeTIL. The prognostic value of CD8 + MeTIL and its predictive value for immunotherapy response were investigated using multiple melanoma cohorts. Results: We successfully constructed the CD8 + MeTIL signature based on four DMPs. The survival analyses showed that higher CD8 + MeTIL score was associated with worse survival outcomes in TCGA-SKCM and GSE144487 cohorts. The ROC curve for the predictive analysis revealed that the survival prediction of CD8 + MeTIL score was superior compared with CD8 + TILs (CIBERSORT) and CD8B mRNA expression. Furthermore, we founded that tumors with higher CD8 + MeTIL score were marked with immunosuppressive characteristics, including low immune score and downregulated immune-related pathways. More importantly, the CD8 + MeTIL score showed a potential predictive value for the benefit from immunotherapy in two published cohorts. When combined CD8 + MeTIL with PD-L1 expression, the patient classification showed significantly different immunotherapy response rates and long-term survival outcomes. Conclusions: The CD8 + MeTIL signature might be as a novel method to evaluate CD8 + TILs and guide immunotherapy approaches. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 01715216
- Volume :
- 149
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Journal of Cancer Research & Clinical Oncology
- Publication Type :
- Academic Journal
- Accession number :
- 161608063
- Full Text :
- https://doi.org/10.1007/s00432-022-04566-1