Immunotherapy has produced promising results in treating cancers. Further understanding of the crosstalk between tumor and its immune microenvironment is likely to have an immediate impact on therapeutic intervention as well as the development of markers of drug resistance. One main difficulty in quantifying the components of tumor microenvironment is that currently there are considerable technological and analytical barriers to assessing and measuring tumor immunity in situ. In this work, we propose to improve the prediction of cell mixtures by both gene expression and epigenetic information. The vast amount of DNA methylation data has been collected in public domain but remains under-analyzed and largely disconnected. No studies have yet investigated the value of using existing methylation panels for immune cell deconvolution in tumor tissues. In our preliminary data, we have observed a strong association between DNA methylation probes and immune signatures such as total TCR expression and tumor infiltrates estimation in melanoma and breast cancer. We have built a more rigorous prediction model based on methylation markers and to extend the analyses to all major cancer types. The results will be externally validated with pooled data from published studies with eligible methylation assay and immune signature measurements. We work closely with immunology scientists to perform a critical evaluation of the robustness and reproducibility of the predictive models. Results of the study, if validated, will have immediate clinical application in screening patient immunity, and will further support the hypothesis that the DNA methylome adds a new dimension to the pan-omic snapshot of cancer immunity and tumor microenvironment. Based on the proposed analytical framework, future prospective studies can be developed using newer methylation platforms—to compare patient groups with different immune conditions and patients in different stages of treatment.

Citation Format: Xuefeng Wang, Cong Liang. Comprehensive analysis of tumor immunity by integrating transcriptome and methylome [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3390.