Background/Objectives:Soft tissue sarcomas (STS) remain a therapeutic challenge due to their limited response to radiation and conventional chemotherapies. While recent advances in immunotherapy have improved outcomes in several cancers, these strategies have been largely disappointing in STS patients. Naturally occurring STS in dogs have been suggested as a spontaneous, immunocompetent model of human STS, but further characterization of its tumor immune microenvironment is needed to validate its relevance. This study aimed to identify the shared immune-related components of canine and human STS and to determine how these factors influence the tumor biology, progression, and prognosis.Results:Data from 75 dogs with STS was analyzed. In addition, we characterized the tumor immune microenvironment using immunohistochemistry and compared gene expression between canine and human STS. Progression-free survival and time to metastasis was significantly longer in castrated males in comparison to females. In addition, dogs with appendicular tumors had better progression- and recurrence-free survival, whereas tumor recurrence following surgical excision was associated with a shorter time to metastasis. Immunohistochemistry revealed infiltration of CD204+cells in most of the tumors examined, and disease-free intervals were shorter in dogs with tumors exhibiting FOXP3+cell infiltration. Gene expression profiling demonstrated similarities between canine STS and human undifferentiated pleomorphic sarcomas, with MYC dysregulation emerging as a poor prognostic indicator for dogs.Conclusions:The comparative analysis between the human and canine STS microenvironment offers a valuable insight into the clinical behavior and immune landscape of canine STS, underscoring its potential as a relevant preclinical model for the translation and development of future immunotherapies.
背景/目的：软组织肉瘤（STS）因对放疗和常规化疗反应有限，仍是治疗难题。尽管免疫疗法的最新进展已改善多种癌症的预后，但这些策略在STS患者中效果普遍不佳。犬类自发性STS被认为是人类STS的自发性免疫活性模型，但需进一步明确其肿瘤免疫微环境特征以验证其相关性。本研究旨在识别犬类与人类STS共有的免疫相关成分，并探究这些因素如何影响肿瘤生物学特性、进展及预后。结果：本研究分析了75只STS患犬的数据，并通过免疫组化技术表征肿瘤免疫微环境，同时比较了犬类与人类STS的基因表达差异。结果显示，去势雄性犬的无进展生存期和转移时间显著长于雌性犬。此外，肢体肿瘤患犬的无进展生存期和无复发生存期更优，而手术切除后肿瘤复发与更短的转移时间相关。免疫组化分析显示，大多数受检肿瘤中存在CD204+细胞浸润，且存在FOXP3+细胞浸润的患犬无病生存期更短。基因表达谱分析表明，犬类STS与人类未分化多形性肉瘤具有相似性，其中MYC基因失调成为犬类不良预后的指标。结论：人类与犬类STS微环境的比较分析为理解犬类STS的临床行为及免疫特征提供了重要视角，凸显了其作为转化研究和未来免疫疗法开发相关临床前模型的潜力。
The Immune Landscape of Canine Soft Tissue Sarcomas as a Model for Human Soft Tissue Sarcomas
肿瘤(癌症)患者之家