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Vaccines 2015, 3(3), 771-802; doi:10.3390/vaccines3030771

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

1
University of Colorado School of Medicine, 12800 East 19th Avenue, Mail Stop 8333, Aurora, CO 80045, USA
2
Center for Genes, Environment and Health, National Jewish Health, Denver, CO 80206, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Mary Lenora (Nora) Disis
Received: 3 August 2015 / Revised: 9 September 2015 / Accepted: 10 September 2015 / Published: 17 September 2015
(This article belongs to the Special Issue Cancer Vaccines)
View Full-Text   |   Download PDF [450 KB, uploaded 24 September 2015]   |  

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. View Full-Text
Keywords: tumor-infiltrating T cells; TIL; transcriptional regulation; T cell dysfunction; T cell hypofunction; anergy; tolerance; exhaustion; NF-κB; NFAT; PD-1; pathway analysis; transcriptome analysis; cancer immunotherapy tumor-infiltrating T cells; TIL; transcriptional regulation; T cell dysfunction; T cell hypofunction; anergy; tolerance; exhaustion; NF-κB; NFAT; PD-1; pathway analysis; transcriptome analysis; cancer immunotherapy
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Waugh, K.A.; Leach, S.M.; Slansky, J.E. Targeting Transcriptional Regulators of CD8+ T Cell Dysfunction to Boost Anti-Tumor Immunity. Vaccines 2015, 3, 771-802.

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