DNA methylation-based signature of CD8+ tumor-infiltrating lymphocytes enables evaluation of immune response and prognosis in colorectal cancer

• DOI: 10.1136/jitc-2021-002671
• Publication Date: 2021-09-21T17:01:41Z
• Authors: Qi Zou; Xiaolin Wang; Donglin Ren; Bang Hu; Guannan Tang; Yu Zhang; Meijin Huang; Rish K Pai; Daniel D Buchanan; Aung Ko Win; Polly A Newcomb; William M Grady; Huichuan Yu; Yanxin Luo
• Keywords: Tumor-infiltrating lymphocytes; Gene signature

Background Tumor-infiltrating lymphocytes (TILs), especially CD8+ TILs, can be used for predicting immunotherapy responsiveness and survival outcome. However, the evaluation of TILs currently relies on histopathological methodology with high variability. We therefore aimed to develop a DNA methylation signature (CD8+ MeTIL) that could evaluate immune response prognosis in colorectal cancer (CRC). Methods A MeTIL score was constructed by using T cell-specific differentially methylated positions (DMPs) were identified from Illumina EPIC arrays. Immune cells, colon epithelial two CRC cohorts (n=282 335) PCR-based assay quantitative analysis at single-base resolution (QASM) determine CD8 + score. Results Three DMPs construct score, which showed dramatic discriminability between cells other cells. The QASM we developed markers measure distributions fully quantitative, accurate, simple manner. determined strong association histopathology-based TIL counts gene expression-based marker. Furthermore, low (enriched TILs) associated MSI-H tumors predicted better cohorts. Conclusions This study methylation-based reliable CRC. approach has potential tool investigations biomarker therapeutic approaches, including immunotherapy.