Comparative Immunogenomics of Canine Natural Killer Cells as Immunotherapy Target

• Published in: Frontiers in immunology Vol. 12; p. 670309
• Main Authors: Gingrich, Alicia A, Reiter, Taylor E, Judge, Sean J, York, Daniel, Yanagisawa, Mio, Razmara, Aryana, Sturgill, Ian, Basmaci, Ugur Nur, Brady, Rachel V, Stoffel, Kevin, Murphy, William J, Rebhun, Robert B, Brown, C Titus, Canter, Robert J
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 14.09.2021
• Subjects: Administration, Inhalation; Adult; Aged; Animals; Blood Donors; Bone Neoplasms - genetics; Bone Neoplasms - immunology; Bone Neoplasms - pathology; Bone Neoplasms - veterinary; canine; comparative oncology; Dog Diseases - genetics; Dog Diseases - immunology; Dog Diseases - therapy; Dogs; Female; Gene Expression Regulation, Neoplastic - immunology; Healthy Volunteers; Humans; Immunologic Factors - administration & dosage; Immunology; Immunotherapy - methods; immunotherapy, osteosarcoma; Interleukin-15 - administration & dosage; K562 Cells; Killer Cells, Natural - immunology; Lung Neoplasms - immunology; Lung Neoplasms - secondary; Lung Neoplasms - therapy; Lung Neoplasms - veterinary; Male; Melanoma - genetics; Melanoma - immunology; Melanoma - pathology; Melanoma - veterinary; Mice; Mice, Inbred C57BL; Middle Aged; natural killer cells; Osteosarcoma - genetics; Osteosarcoma - immunology; Osteosarcoma - pathology; Osteosarcoma - veterinary; single cell; Transcriptome; Treatment Outcome; Young Adult; natural killer cells; single cell; canine; immunotherapy, osteosarcoma; comparative oncology
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2021.670309

Natural killer (NK) cells are key effectors of the innate immune system, but major differences between human and murine NK cells have impeded translation. Outbred dogs offer an important link for studies of NK biology and immunotherapy. We analyzed gene expression of putative NK populations from healthy dogs and dogs with naturally-occurring cancers examining differential gene expression across multiple conditions, including steady-state, activation with cytokines and co-culture, and activation with inhaled IL-15 in dogs receiving IL-15 immunotherapy. We also compared dog, mouse and human CD3-NKp46+ NK cells using a novel orthologous transcriptome. Distinct transcriptional profiles between NK populations exist between conditions and versus treatments. In cross-species analysis, canine NK cells were globally more similar to human NK cells than mice. These data define canine NK cell gene expression under multiple conditions and across species, filling an important gap in translational NK studies.