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

Derré, Laurent; Rivals, Jean-Paul; Jandus, Camilla; Pastor, Sonia; Rimoldi, Donata; Romero, Pedro; Michielin, Olivier; Olive, Daniel; Speiser, Daniel E (2010). BTLA mediates inhibition of human tumor-specific CD8+ T cells that can be partially reversed by vaccination. Journal of clinical investigation, 120(1), pp. 157-67. Ann Arbor, Mich.: American Society for Clinical Investigation 10.1172/JCI40070

[img]
Preview
Text
render.pdf - Published Version
Available under License Publisher holds Copyright.

Download (2MB) | Preview

The function of antigen-specific CD8+ T cells, which may protect against both infectious and malignant diseases, can be impaired by ligation of their inhibitory receptors, which include CTL-associated protein 4 (CTLA-4) and programmed cell death 1 (PD-1). Recently, B and T lymphocyte attenuator (BTLA) was identified as a novel inhibitory receptor with structural and functional similarities to CTLA-4 and PD-1. BTLA triggering leads to decreased antimicrobial and autoimmune T cell responses in mice, but its functions in humans are largely unknown. Here we have demonstrated that as human viral antigen-specific CD8+ T cells differentiated from naive to effector cells, their surface expression of BTLA was gradually downregulated. In marked contrast, human melanoma tumor antigen-specific effector CD8+ T cells persistently expressed high levels of BTLA in vivo and remained susceptible to functional inhibition by its ligand herpes virus entry mediator (HVEM). Such persistence of BTLA expression was also found in tumor antigen-specific CD8+ T cells from melanoma patients with spontaneous antitumor immune responses and after conventional peptide vaccination. Remarkably, addition of CpG oligodeoxynucleotides to the vaccine formulation led to progressive downregulation of BTLA in vivo and consequent resistance to BTLA-HVEM-mediated inhibition. Thus, BTLA activation inhibits the function of human CD8+ cancer-specific T cells, and appropriate immunotherapy may partially overcome this inhibition.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology

UniBE Contributor:

Jandus, Camilla

ISSN:

0021-9738

Publisher:

American Society for Clinical Investigation

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:09

Last Modified:

08 Sep 2015 03:20

Publisher DOI:

10.1172/JCI40070

PubMed ID:

20038811

Web of Science ID:

000273495700021

BORIS DOI:

10.7892/boris.888

URI:

https://boris.unibe.ch/id/eprint/888 (FactScience: 201180)

Actions (login required)

Edit item Edit item
Provide Feedback