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

Area of Science:

• Immunology
• Veterinary Oncology
• Cancer Immunotherapy

Background:

• Programmed death receptor 1 (PD-1) is a co-inhibitory checkpoint molecule that induces T cell exhaustion upon binding its ligand PD-L1.
• PD-1 blocking antibodies have shown significant success in human cancer treatment, leading to durable responses in advanced cancers.

Purpose of the Study:

• To evaluate monoclonal antibodies targeting canine PD-1 for their ability to bind T cells and induce functional activation.
• To assess the potential of canine PD-1 antibodies as a novel cancer immunotherapy for dogs.

Main Methods:

• Quantified PD-1 expression on canine T cells (CD4 and CD8) from healthy dogs and dogs with cancer.
• Assessed the impact of PD-1 antibodies on T cell proliferation and interferon-gamma (IFN-γ) production.
• Investigated the ability of PD-1 antibodies to reverse T cell suppression induced by canine soluble PD-L1, tumor cells, and tumor explant fragments.

Main Results:

• PD-1 was expressed on 5-10% of CD4 T cells and 20-25% of CD8 T cells in healthy dogs, with upregulation in dogs with cancer.
• Canine PD-1 antibodies significantly enhanced T cell activation, evidenced by increased proliferation and IFN-γ production.
• PD-1 antibodies effectively reversed T cell suppression mediated by canine soluble PD-L1 and tumor tissues.

Conclusions:

• Canine PD-1 antibodies demonstrate T cell binding and functional activation capabilities.
• These antibodies can overcome tumor-induced T cell suppression, indicating their potential as a cancer immunotherapy in veterinary medicine.