Expression profile of immunoregulatory factors in canine tumors

Kohei Murakami, Saki Miyatake, Jiro Miyamae, Kanna Saeki, Mizutani Shinya, Natsuki Akashi, Ikki Mitsui, Kosuke Kobayashi, Kohei Saeki, Noritaka Maeta, Teppei Kanda, Yasuhiko Okamura, Hiroaki Hemmi

Cancers utilize a variety of molecules to escape host immune responses. Better understanding the immune
environment surrounding cancer may facilitate application of innovative cancer immunotherapies, such as immune checkpoint inhibitors, to dogs as well as humans. In this study, we screened the expression of 20 immune
regulatory molecules in diverse canine tumors (n = 59). Quantitative RT-PCR (qPCR) analysis revealed that some
immune regulatory molecules, such as LGALS9 (coding Galectin-9) and CD48, were expressed in most canine
tumors, but other molecules, such as CD274 (coding PD-L1), IL4I1, PVR, TNFSF18, ICOSLG, and TNFSF4, were
rarely expressed. NECTIN2 was highly expressed in epithelial tumors but was low in non-epithelial tumors. In
contrast, VSIR and CD200 expressions were low in epithelial tumors but high in non-epithelial tumors. Interestingly, several tumors expressed distinctive immunoregulatory factors. Hepatocellular carcinomas expressed
FGL1, mast cell tumors expressed PDCD1LG2 (coding PD-L2), transitional cell carcinomas expressed VTCN1
(coding B7x), and lymphomas and squamous cell carcinomas expressed CD70. Consistent with qPCR results,
immunofluorescence staining confirmed that hepatocellular carcinomas expressed FGL-1 protein. Thus, this
study reveals the expression profile of immunoregulatory molecules in canine tumors and opens the door to
better understanding the relationship between canine tumors and host immunity.

Veterinary Immunology and Immunopathology

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