Melanoma in humans and canines is an aggressive and highly metastatic cancer. The mucosal forms in both species share genetic and histopathologic features, making dogs a valuable spontaneous disease animal model. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells of myeloid origin with immunosuppressive capabilities, which are increased in many human cancers and contribute to tumor immune evasion. They are a possible target to improve immunotherapy outcomes. Current information regarding MDSCs in canines is minimal, limiting their use as translational model for the study of MDSCs. The objective of this study was to characterize major MDSCs subsets (monocytic and polymorphonuclear) and the cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 10 (IL-10) and monocyte chemoattractant protein-1 (MCP-1) in canines with malignant melanoma and to evaluate changes in MDSCs and the cytokines over time in response to a GD3-based active immunotherapy. Whole blood and serum collected from 30 healthy controls and 33 patients enrolled in the University of Florida melanoma vaccine trial were analyzed by flow cytometry with canine specific CD11b, MHCII and anti-human CD14 antibodies to assess ostensibly polymorphonuclear-MDSC (CD11b+ MHCII- CD14-) and monocytic-MDSC (CD11b+ MHCII- CD14+) subsets. IL-10, MCP-1 and both MDSCs subsets were significantly elevated in melanoma dogs versus controls. Both MDSCs subsets decreased significantly following GD3-based immunotherapy administration but no significant changes in cytokines were seen over time. To our knowledge, this is the first report documenting increased monocytic-MDSCs in canine melanoma. This is consistent with human malignant melanoma data, supporting dogs as a valuable model for therapeutic intervention studies.

中文翻译：

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接受基于GD3的免疫治疗的恶性黑色素瘤犬中骨髓来源的抑制细胞和细胞因子GM-CSF，IL-10和MCP-1的表征。

人类和犬黑素瘤是一种侵袭性和高度转移性癌症。这两种物种的粘膜形式都具有遗传和组织病理学特征，使狗成为一种有价值的自发性疾病动物模型。髓样来源的抑制细胞（MDSC）是具有免疫抑制能力的异种髓样细胞群体，在许多人类癌症中均增加，并有助于逃避肿瘤。它们是改善免疫治疗结果的可能目标。关于犬中MDSC的最新信息很少，限制了它们用作MDSC研究的翻译模型。这项研究的目的是鉴定主要的MDSC子集（单核和多形核）和细胞因子粒细胞巨噬细胞集落刺激因子（GM-CSF），白细胞介素10（IL-10）和单核细胞趋化蛋白1（MCP-1）在恶性黑色素瘤犬中的作用，并评估基于GD3的主动免疫疗法随时间推移MDSCs和细胞因子的变化。通过流式细胞仪分析犬特异性CD11b，MHCII和抗人CD14抗体，通过流式细胞术分析了从30名健康对照和33名参加佛罗里达大学黑素瘤疫苗试验的患者中收集的全血和血清，从表面上评估了多形核-MDSC（CD11b + MHCII- CD14- ）和单核细胞MDSC（CD11b + MHCII- CD14 +）子集。与对照组相比，黑色素瘤犬的IL-10，MCP-1和两个MDSCs亚群均显着升高。基于GD3的免疫疗法给药后，两个MDSCs亚群均显着下降，但随着时间的推移，未观察到细胞因子的显着变化。据我们所知，这是第一篇报道犬黑色素瘤单核细胞MDSCs增加的报告。这与人类恶性黑色素瘤数据一致，支持狗作为治疗干预研究的有价值模型。