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Cell-Intrinsic Barriers of T Cell-Based Immunotherapy.

ABSTRACT: 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.

SUBMITTER: Ghoneim HE

PROVIDER: S-EPMC5135632 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Cell-Intrinsic Barriers of T Cell-Based Immunotherapy.

Ghoneim Hazem E HE Zamora Anthony E AE Thomas Paul G PG Youngblood Ben A BA

Trends in molecular medicine 20161104 12

Prolonged exposure of CD8<sup>+</sup> 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 al ...[more]

PMID: 27825667

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