PD-1 expression by canine T cells and functional effects of PD-1 blockade.

Abstract

The co-inhibitory checkpoint molecule programmed death receptor 1 (PD-1) can trigger T cell functional exhaustion upon binding to its ligand PD-L1 expressed on tumour cells or macrophages. PD-1 blocking antibodies have generated remarkable results in human cancer patients, including inducing durable responses in a number of advanced cancers. Therefore, monoclonal antibodies specific for canine PD-1 were assessed for T cell binding and induction of functional activation. A total of 5-10% of CD4 T cells and 20-25% of CD8 T cells from healthy dogs expressed PD-1, and PD-1 expression was upregulated on T cells from dogs with cancer. Functionally, PD-1 antibodies significantly enhanced T-cell activation, as assessed by proliferation and interferon-gamma (IFN-γ) production. PD-1 antibodies also reversed T-cell suppression induced by canine soluble PD-L1 and by tumour cells and tumour explant fragments. These findings indicate that PD-1 antibodies have potential for use in cancer immunotherapy in dogs.

• Authors: J Coy, A Caldwell, L Chow, A Guth, S Dow
• Journal: Veterinary and comparative oncology (Vet Comp Oncol) Vol. 15 Issue 4 Pg. 1487-1502 (Dec 2017) ISSN: 1476-5829 [Electronic] England
• PMID: 28120417 (Publication Type: Journal Article)
• Copyright: © 2017 John Wiley & Sons Ltd.

Chemical References

• Programmed Cell Death 1 Receptor
• Interferon-gamma

Topics

• Animals
• Blotting, Western (veterinary)
• CD4-Positive T-Lymphocytes (metabolism)
• CD8-Positive T-Lymphocytes (metabolism)
• Dogs
• Flow Cytometry (veterinary)
• Interferon-gamma (metabolism)
• Myeloid Cells (metabolism)
• Programmed Cell Death 1 Receptor (antagonists & inhibitors, metabolism)
• T-Lymphocytes (metabolism)