Genetic and Epigenetic Regulation of PD-1 Expression

作者：Alexander P. R. Bally, James W. Austin, Jeremy M. Boss · 发表于：The Journal of Immunology · 年份：2016 · DOI：10.4049/jimmunol.1502643 · 被引用次数：254 · 研究领域：Immune Cell Function and Interaction、Cancer Immunotherapy and Biomarkers、Immunotherapy and Immune Responses

The inhibitory immune receptor programmed cell death-1 (PD-1) is intricately regulated. In T cells, PD-1 is expressed in response to most immune challenges, but it is rapidly downregulated in acute settings, allowing for normal immune responses. On chronically stimulated Ag-specific T cells, PD-1 expression remains high, leading to an impaired response to stimuli. Ab blockade of PD-1 interactions during chronic Ag settings partially restores immune function and is now used clinically to treat a variety of devastating cancers. Understanding the regulation of PD-1 expression may be useful for developing novel immune-based therapies. In this review, the molecular mechanisms that drive dynamic PD-1 expression during acute and chronic antigenic stimuli are discussed. An array of cis-DNA elements, transcription factors, and epigenetic components, including DNA methylation and histone modifications, control PD-1 expression. The interplay between these regulators fine-tunes PD-1 expression in different inflammatory environments and across numerous cell types to modulate immune responses.