作者
Helen Loo Yau, Emma Bell, Ilias Ettayebi, Felipe Campos de Almeida, Giselle M Boukhaled, Shu Yi Shen, David Allard, Beatriz Morancho, Sajid A Marhon, Charles A Ishak, Isabela M Gonzaga, Tiago da Silva Medina, Rajat Singhania, Ankur Chakravarthy, Raymond Chen, Parinaz Mehdipour, Sandra Pommey, Christian Klein, Gustavo P Amarante-Mendes, David Roulois, Joaquín Arribas, John Stagg, David G Brooks, Daniel D De Carvalho
发表日期
2021/4/1
期刊
Molecular cell
卷号
81
期号
7
页码范围
1469-1483. e8
出版商
Elsevier
简介
We demonstrate that DNA hypomethylating agent (HMA) treatment can directly modulate the anti-tumor response and effector function of CD8+ T cells. In vivo HMA treatment promotes CD8+ T cell tumor infiltration and suppresses tumor growth via CD8+ T cell-dependent activity. Ex vivo, HMAs enhance primary human CD8+ T cell activation markers, effector cytokine production, and anti-tumor cytolytic activity. Epigenomic and transcriptomic profiling shows that HMAs vastly regulate T cell activation-related transcriptional networks, culminating with over-activation of NFATc1 short isoforms. Mechanistically, demethylation of an intragenic CpG island immediately downstream to the 3′ UTR of the short isoform was associated with antisense transcription and alternative polyadenylation of NFATc1 short isoforms. High-dimensional single-cell mass cytometry analyses reveal a selective effect of HMAs on a subset of …
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HL Yau, E Bell, I Ettayebi, FC de Almeida… - Molecular cell, 2021