Kret Zaina S, Sweder Ryan J, Pollock Raphael, Tinoco Gabriel
The University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA.
The Ohio State University College of Arts and Sciences and College of Medicine, Columbus, OH, USA.
Target Oncol. 2025 Apr 27. doi: 10.1007/s11523-025-01145-5.
Soft-tissue sarcomas represent a diverse group of rare malignancies originating from mesenchymal tissue, accounting for less than 1% of adult cancers in the USA. With over 13,000 new cases and around 5350 deaths annually, patients with metastatic soft-tissue sarcomas face limited therapeutic options and an estimated median overall survival of 18 months. While immunotherapy has demonstrated effectiveness in several cancers, its application in soft-tissue sarcomas remains challenging owing to the tumors' largely "cold" immunological environment, characterized by low levels of tumor-infiltrating lymphocytes and a lack of soft-tissue sarcoma-specific biomarkers. This review examines potential mechanisms underlying immunotherapy resistance in soft-tissue sarcomas, including the complex interplay between innate and adaptive immunity, the tumor microenvironment, and the role of immune-related genes. Despite preliminary findings suggesting correlations between immune profiles and histological subtypes, consistent biomarkers for predicting immunotherapeutic responses across soft-tissue sarcoma types are absent. Emerging strategies focus on converting "cold" tumors to "hot" tumors, enhancing their susceptibility to immunologic activation. While research is ongoing, personalized treatment approaches may offer hope for overcoming the inherent heterogeneity and resistance seen in soft-tissue sarcomas, ultimately aiming to improve outcomes for affected patients.
软组织肉瘤是源自间充质组织的一组罕见的异质性恶性肿瘤，在美国占成人癌症的比例不到1%。每年有超过13000例新发病例和约5350例死亡病例，转移性软组织肉瘤患者面临的治疗选择有限，估计总中位生存期为18个月。虽然免疫疗法已在几种癌症中显示出有效性，但由于肿瘤在很大程度上处于“冷”免疫环境，其特征为肿瘤浸润淋巴细胞水平低且缺乏软组织肉瘤特异性生物标志物，因此在软组织肉瘤中的应用仍然具有挑战性。本综述探讨了软组织肉瘤中免疫治疗耐药的潜在机制，包括先天免疫和适应性免疫之间的复杂相互作用、肿瘤微环境以及免疫相关基因的作用。尽管初步研究结果表明免疫特征与组织学亚型之间存在相关性，但缺乏可预测不同类型软组织肉瘤免疫治疗反应的一致性生物标志物。新兴策略集中于将“冷”肿瘤转变为“热”肿瘤，增强其对免疫激活的敏感性。虽然研究仍在进行中，但个性化治疗方法可能为克服软组织肉瘤中固有的异质性和耐药性带来希望，最终目标是改善受影响患者的治疗结果。
