Diffuse large B-cell lymphoma is one of the most common cancers in dogs. Current standard of care for dogs with lymphoma includes doxorubicin-based chemotherapy protocols, which result in clinical remission rates of up to 90%. However, relapses are common, and reported mean remission duration ranges from 8 to 12 months.1–6 Therefore, novel therapies are necessary to improve remission duration for dogs with lymphoma.
Immune checkpoint inhibitors have emerged as promising novel treatments for human patients with DLBCL and other cancers. A therapeutic target of particular interest in checkpoint inhibitor therapy is the interaction of PD-1 with PD-L1. Programmed cell death protein-1 is a T-cell surface protein that is part of the B7 receptor family. Its interaction with PD-L1 has an important role in attenuating effector T-cell responses to protect against autoimmune disease. Programmed cell death ligand-1 is overexpressed in many types of cancer and leads to T-cell exhaustion and tumoral immune evasion.7,8 Specifically, in human medicine, overexpression of PD-L1 has been described in patients with melanoma,9 non–small cell lung cancer,10 breast cancer,11 bladder cancer,12 renal carcinoma,13 hepatocellular carcinoma,14 esophageal cancer,15 gastric cancer,16 pancreatic cancer,17 and lymphoma.18 For patients with those types of cancers, including DLBCL, overexpression of PD-L1 is associated with a poor clinical outcome.18 However, the recent development and use of anti–PD-L1 therapies have resulted in clinical responses and improved survival times for human patients with cancer, including those who have previously received multiple treatments and those with advanced disease.19–21
For dogs with DLBCL, tumor expression of PD-L1must be documented before it can be rationally targeted by anti–PD-L1 therapy. Currently, information regarding PD-L1 expression in veterinary patients with naturally occurring cancer, including dogs with DLBCL, is limited. Studies22—24 in which PD-L1 expression was evaluated in multiple types of canine tumors, including a small number of lymphomas, have yielded conflicting results. The primary objective of the study reported here was to quantify PD-L1 expression in the tumors of a larger, more homogenous population of dogs with DLBCL than previously evaluated.24 A secondary objective was to determine whether PD-L1 expression was associated with PFST following chemotherapy in dogs with DLBCL. We hypothesized that expression of PD-L1 in canine DLBCL tumors would vary and that PD-L1 expression would be negatively associated with PFST.
Supported by a Graduate Student Competitive Research Award from the Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Purdue University.
The authors declare that there were no conflicts of interest.
Presented in abstract form at the Annual Conference of the Veterinary Cancer Society, Orlando, Fla, October 2016.
Cyclophosphamide, doxorubicin, vincristine, and prednisone
Diffuse large B-cell lymphoma
Glyceraldehyde 3-phosphate dehydrogenase
Programmed cell death protein-1
Programmed cell death ligand-1
Progression-free survival time
Quantitative real-time PCR
Transitional cell carcinoma
World Health Organization
TRIzol reagent, Invitrogen Corp, Carlsbad, Calif.
Nanodrop, Thermo Fisher Scientific, Waltham, Mass.
SuperScript VILO Master Mix, Invitrogen Corp, Carlsbad, Calif.
Stratagene Mx3000 qPCR system, Agilent Technologies Inc, Santa Clara, Calif.
TaqMan probes, Invitrogen Corp, Carlsbad, Calif.
Basic Local Alignment Search Tool (BLAST), US National Library of Medicine, Bethesda, Md. Available at: blast.ncbi.nlm.nih.gov/Blast.cgi. Accessed July 13, 2017.
Life Technologies, Carlsbad, Calif.
FAM, Life Technologies, Carlsbad, Calif.
VIC, Life Technologies, Carlsbad, Calif.
MGB-NFQ, Invitrogen Corp, Carlsbad, Calif.
R&D Systems Inc, Minneapolis, Minn.
StataSE, version 13.1, StataCorp LP, College Station, Tex.
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