Cell-Intrinsic Barriers of T Cell-Based Immunotherapy.
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.
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA; Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
Hazem E
HE
Ghoneim
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Anthony E
AE
Zamora
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Paul G
PG
Thomas
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA. Electronic address: benjamin.youngblood@stjude.org.
Ben A
BA
Youngblood
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005818:Genetic Engineering / Q000379:methods; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D016219:Immunotherapy, Adoptive / Q000379:methods; D009369:Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation
D011948:Receptors, Antigen, T-Cell
DNA methylation.; T cell exhaustion; chimeric antigen receptor T cells; epigenetics; histone modification; immune checkpoint blockade