Cell-Intrinsic Barriers of T Cell-Based Immunotherapy

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• 作者：Hazem E. Ghoneim¹ ; ² ; Anthony E. Zamora¹ ; Paul G. Thomas¹ ; Ben A. Youngblood¹ ; ^{benjamin.youngblood@stjude.org}
• 关键词：immune checkpoint blockade ; chimeric antigen receptor T cells ; T cell exhaustion ; epigenetics ; histone modification ; DNA methylation.
• 刊名：Trends in Molecular Medicine
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：22
• 期：12
• 页码：1000-1011
• 全文大小：1859 K
• 卷排序：22

文摘

Prolonged exposure of CD8+ T cells to their cognate antigen can result in exhaustion of effector functions enabling the persistence of infected or transformed cells. Recent advances in strategies to rejuvenate host effector function using Immune Checkpoint Blockade have resulted in tremendous success towards the treatment of several cancers. However, it is unclear if T cell rejuvenation results in long-lived antitumor functions. Emerging evidence suggests that T cell exhaustion may also represent a significant impediment in sustaining long-lived antitumor activity by chimeric antigen receptor T cells. Here, we discuss current findings regarding transcriptional regulation during T cell exhaustion and address the hypothesis that epigenetics may be a potential barrier to achieving the maximum benefit of T cell-based immunotherapies.