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Vaccines (Basel). 2015 Sep 17;3(3):771-802. doi: 10.3390/vaccines3030771.

Targeting Transcriptional Regulators of CD8+ T Cell Dysfunction to Boost Anti-Tumor Immunity.

Author information

1
University of Colorado School of Medicine, 12800 East 19th Avenue, Mail Stop 8333, Aurora, CO 80045, USA. Katherine.Waugh@UCDenver.edu.
2
Center for Genes, Environment and Health, National Jewish Health, Denver, CO 80206, USA. LeachS@NJHeath.org.
3
University of Colorado School of Medicine, 12800 East 19th Avenue, Mail Stop 8333, Aurora, CO 80045, USA. Jill.Slansky@UCDenver.edu.

Abstract

Transcription is a dynamic process influenced by the cellular environment: healthy, transformed, and otherwise. Genome-wide mRNA expression profiles reflect the collective impact of pathways modulating cell function under different conditions. In this review we focus on the transcriptional pathways that control tumor infiltrating CD8+ T cell (TIL) function. Simultaneous restraint of overlapping inhibitory pathways may confer TIL resistance to multiple mechanisms of suppression traditionally referred to as exhaustion, tolerance, or anergy. Although decades of work have laid a solid foundation of altered transcriptional networks underlying various subsets of hypofunctional or "dysfunctional" CD8+ T cells, an understanding of the relevance in TIL has just begun. With recent technological advances, it is now feasible to further elucidate and utilize these pathways in immunotherapy platforms that seek to increase TIL function.

KEYWORDS:

NF-κB; NFAT; PD-1; T cell dysfunction; T cell hypofunction; TIL; anergy; cancer immunotherapy; exhaustion; pathway analysis; tolerance; transcriptional regulation; transcriptome analysis; tumor-infiltrating T cells

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