Abstract
Programmed death 1 (PD-1), an immunoinhibitory receptor, and programmed death ligand 1 (PD-L1), its ligand, together induce the “exhausted” status in antigen-specific lymphocytes and are thus involved in the immune evasion of tumor cells. In this study, canine PD-1 and PD-L1 were molecularly characterized, and their potential as therapeutic targets for canine tumors was discussed. The canine PD-1 and PD-L1 genes were conserved among canine breeds. Based on the sequence information obtained, the recombinant canine PD-1 and PD-L1 proteins were constructed; they were confirmed to bind each other. Antibovine PD-L1 monoclonal antibody effectively blocked the binding of recombinant PD-1 with PD-L1–expressing cells in a dose-dependent manner. Canine melanoma, mastocytoma, renal cell carcinoma, and other types of tumors examined expressed PD-L1, whereas some did not. Interestingly, anti-PD-L1 antibody treatment enhanced IFN-γ production from tumor-infiltrating cells. These results showed that the canine PD-1/PD-L1 pathway is also associated with T-cell exhaustion in canine tumors and that its blockade with antibody could be a new therapeutic strategy for canine tumors. Further investigations are needed to confirm the ability of anti-PD-L1 antibody to reactivate canine antitumor immunity in vivo, and its therapeutic potential has to be further discussed.
Highlights
Cancer has been a major cause of death in dogs and has surpassed infectious diseases
Clinical trials targeting the Programmed death 1 (PD-1)/PD-L pathway by using PD-1 antibody are ongoing for cancer therapy [19,39]
There has been no report demonstrating that the blockade targeting the PD-1/PD-L pathway might show potential for development of new therapies against canine tumors
Summary
Cancer has been a major cause of death in dogs and has surpassed infectious diseases. According to a recent report, 27% of overall dog deaths is due to cancer [1]. Current clinical approaches for canine cancer are surgical, chemotherapeutic, and radiation therapies, as in humans. In some cases of dog cancers, it is difficult to treat them by only using existing therapeutic methods because of the severe stress, adverse effect, and/or difficulties in approaching the tumor sites. The sensitivities to the chemo/radiotherapies can differ dependent on the tumor types. It is worth investigating the efficacy of novel approaches against canine cancer, including immunotherapy, as this may lead to the development of more effective therapies that can induce tumor remission
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