BTLA mediates inhibition of human tumor-specific CD8⁺ T cells that can be partially reversed by vaccination

Derré L, et al. 2010 J. Clin. Invest 120, 157-167

Speaker: Jhen-Yu Ke (柯貞妤)                                                Time:14:00~15:00, Mar 10, 2010

Commentator: Dr. Jyh-Wei Shin (辛致煒 老師)                 Place: Room 601

Abstract:

Antigen-specific CD8⁺ T cells play a pivotal role in the host response to viral infections and cancers¹. Previous studies have showed that the binding of their inhibitory coreceptors, such as CTL-associated protein 4 (CTLA-4) and programmed cell death 1 (PD-1), could suppress the function of antigen-specific CD8⁺ T cells². Recently, there was a novel inhibitory receptor, B and T lymphocyte attenuator (BTLA) with structural and functional similarities to CTLA-4 and PD-1, be indentified². The ligation of BTLA by its ligand herpes virus entry mediator ( HVEM) resulted in decreased T cell proliferation and cytokine production in mice³. However, only little is known about the role and function of BTLA in humans. In this paper, the authors show for the first time that decreased BTLA expression correlated with CD8⁺ T cell differentiation. In marked contrast, tumor-specific CD8⁺ T cells persistently expressed BTLA despite effector cell differentiation in unvaccinated melanoma patients and after conventional peptide vaccination. Surprisingly, after vaccination with CpGoligodeoxynucleotides as adjuvant, tumor-specific CD8⁺ T cells downregulated BTLA in vivo and became independent of BTLA-HVEM-mediated inhibition. Therefore, the authors’ findings provide a suitable immunotherapy that may partially reverse BTLA-mediated inhibition.

References:

1. Appay V, et al. 2008. CD8⁺ T cell efficacy in vaccination and disease Nat.Med.4, 623-628
2. Peggs KS, et al. 2008. Cell intrinsic mechanisms of T-cell inhibition and application to cancer therapy. Immunol Rev. 224, 141-165
3. Watanabe N, et al. 2003. BTLA is a lymphocyte inhibitory receptor with similarities to CTLA-4 and PD-1. Nat Immunol.4, 670-679