Putting the brakes on BTLA in T cell-mediated cancer immunotherapy

J Clin Invest. 2010 Jan;120(1):76-80. doi: 10.1172/JCI41811. Epub 2009 Dec 28.


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.

Publication types

  • Comment
  • Research Support, N.I.H., Extramural

MeSH terms

  • Antigens, CD / physiology
  • Antigens, Neoplasm / physiology
  • CTLA-4 Antigen
  • GPI-Linked Proteins
  • Humans
  • Immunotherapy
  • MART-1 Antigen
  • Neoplasm Proteins / physiology
  • Neoplasms / immunology
  • Neoplasms / therapy*
  • Oligodeoxyribonucleotides / pharmacology
  • Receptors, Immunologic / analysis
  • Receptors, Immunologic / physiology*
  • T-Lymphocytes / immunology*


  • Antigens, CD
  • Antigens, Neoplasm
  • BTLA protein, human
  • CD160 protein, human
  • CPG-oligonucleotide
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • GPI-Linked Proteins
  • MART-1 Antigen
  • MLANA protein, human
  • Neoplasm Proteins
  • Oligodeoxyribonucleotides
  • Receptors, Immunologic