Expert lecture maps DNA methylation programs that drive CD8 T cell exhaustion and limit immunotherapy

An ImmuneZoom expert lecture on YouTube, 53 minutes long, explains how functional and exhausted CD8 T cells acquire distinct DNA methylation programs, with chronic antigen exposure in tumors and chronic viral infection imprinting an exhausted epigenetic state that erodes responses to checkpoint blockade and CAR-T over time. It distinguishes post-treatment acquired exhaustion from pre-existing exhaustion in CAR-T and TIL products before therapy, implying different intervention windows. Targeted epigenetic reprogramming may restore T cell persistence, but clinical efficacy and safety remain to be validated.