Epigenetic inflexibility of exhausted T cells limits durability of reinvigoration by PD-1 blockade. Mus musculus

Upon PD-1 pathway blockade,the epigenetic landscape of exhausted cells was only minimally remodeled consistent with lineage commitment and re-exhaustion of these cells over time. Overall design: Epigenetic profiling of Exhausted T cells & examinaton of epigenetic changes associated with PD-pathway blockade by ATAC-seq using the mouse model of chronic infection with lymphocytic choriomeningitis virus (LCMV)

经PD-1通路阻断（PD-1 pathway blockade）处理后，耗竭细胞（exhausted cells）的表观遗传景观（epigenetic landscape）仅发生轻微重塑，该变化与这些细胞的谱系定型（lineage commitment）及随时间推移出现的再次耗竭（re-exhaustion）状态相一致。
整体实验设计：通过构建淋巴细胞性脉络丛脑膜炎病毒（Lymphocytic choriomeningitis virus, LCMV）慢性感染小鼠模型，采用ATAC-seq技术对耗竭T细胞（Exhausted T cells）开展表观基因组分析，并检测与PD通路阻断（PD-pathway blockade）相关的表观遗传变化。