Journal
CLINICAL IMMUNOLOGY
Volume 183, Issue -, Pages 167-173Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.clim.2017.09.002
Keywords
PD-1; BTLA; TIM-3; CD160; LAG-3; CTLA-4; Immune checkpoints; Coinhibitory receptors; T cell exhaustion; HIV-1
Categories
Funding
- Boehringer Ingelheim RCV
- Austrian Science Fund (FWF) [W1248] Funding Source: Austrian Science Fund (FWF)
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Persistent stimulation with antigens derived from viruses that establish chronic infections or tumour antigens results in the exhaustion of T cells. Coinhibitory receptors like PD-1 and CTLA-4 function as immune checkpoints on exhausted T cells. Blocking these molecules with antibodies improve immunity to cancer cells. Immune checkpoint inhibitors targeting other coinhibitory receptors might have a similar role in improving T cell function and thus also utility in cancer therapy. Using HIV-specific T cells as a model for exhaustion we have evaluated the capacity of antibodies targeting TIM-3, BTLA, CD160, LAG-3 and CTLA-4 alone or in combination with a PD-1 antibody to enhance proliferation and cytokine production in response to Gag and Nef peptides. Antibodies targeting BTLA and TIM-3 enhanced CD8 T cell proliferation. Moreover, our results indicate that blocking BTLA and TIM-3 in combination with PD-1 might be especially effective in enhancing responses of exhausted human T cells. (C) 2017 Elsevier Inc. All rights reserved.
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