Abstract B084: Methylation landscape of tumors associated with antitumor immune signature

Abstract

The most reliable predictive biomarker of cancer immunotherapy is gene expression profile (GEP) of tumor microenvironment. GEPs such as local immune cytolytic activity, interferon-gamma signature, and immune signature score have been reported to represent anti-tumor immune signature. Previously, we reported that immune signature score was positively correlated with tumor mutational burden, but negatively correlated with chromosomal instability (CIN) score, since tumors with high CIN score had significantly low neoantigen burden. However, methylation signature or burden of tumor would also affect antitumor immunogenicity, there has been no analysis reported so far. In the current study, we investigated if methylation landscape of tumor would be associated with GEPs of anti-tumor immune signature using The Cancer Genome Atlas (TCGA) pan-cancer database. In TCGA, 8269 pan-cancer samples had both RNA sequencing data and methylation data using Infinium HumanMethylation450K BeadChip, which were included in the main analysis. Although tumors with high mutational burden (Mu-type) and high CIN burden (C-type) were exclusively classified with negative correlation, methylation burden was not correlated with mutational burden or CIN burden in any pattern. Interestingly, antitumor immune signature measured by local immune cytolytic activity (CytAct) was clearly decreased with high methylational burden, as seen in high CIN burden. Hypermethylation of promoter of genes related to tumor antigen recognition by T-cell such as HLA family, B2M, CD74, and CD274 (PD-L1) were negatively associated with CytAct in pan-cancer analysis. In conclusion, methylation signature of tumor is also associated with antitumor immunogenicity with a negative correlation in general. Further study of whether specific methylation pattern would be associated with anti-PD-1/PD-L1 inhibitors in clinical study would be warranted. Citation Format: Chan-Young Ock, Changhee Park, Kyeonghun Jeong, Sohee Jung, Jeong Mo Bae, Kwangsoo Kim. Methylation landscape of tumors associated with antitumor immune signature [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B084.