Putting the brakes on BTLA in T cell-mediated cancer immunotherapy.
Attenuating coinhibitory molecules for the treatment of cancer is gaining a great deal of attention as a strategy for immunotherapy. The B and T lymphocyte attenuator (BTLA, CD272) is a novel coinhibitory molecule structurally and functionally related to CTLA-4 and PD-1. A study in this issue of the JCI by Derré et al. reveals that BTLA is expressed on virus-specific human CD8+ T cells but is progressively downregulated after their differentiation from a naive to effector phenotype (see the related article beginning on page 157). Surprisingly, tumor-specific human CD8+ T cells continue to express BTLA even after their differentiation to an effector phenotype. Remarkably, vaccination of melanoma patients with CpG led to BTLA downregulation on tumor-specific human CD8+ T cells, concomitant with restoration of their functionality. We discuss these findings in the context of the expanding field of cosignaling molecules and their implications for T cell-based therapies for cancer.
Paulos
Chrystal M
CM
Abramson Family Cancer Research Institute and Department of Pathology and Laboratory Medicine, University of Pennsylvania, 421 Curie Boulevard, Philadelphia, Pennsylvania 19104-6160, USA. chrystal.paulos@gmail.com
June
Carl H
CH
D015703:Antigens, CD / Q000502:physiology; D000951:Antigens, Neoplasm / Q000502:physiology; D060908:CTLA-4 Antigen; D058851:GPI-Linked Proteins; D006801:Humans; D007167:Immunotherapy; D058965:MART-1 Antigen; D009363:Neoplasm Proteins / Q000502:physiology; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000032:analysis / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D000951:Antigens, Neoplasm; C482586:BTLA protein, human; C114505:CD160 protein, human; C408982:CPG-oligonucleotide; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D058851:GPI-Linked Proteins; D058965:MART-1 Antigen; C548667:MLANA protein, human; D009363:Neoplasm Proteins; D009838:Oligodeoxyribonucleotides; D011971:Receptors, Immunologic