Mannah Brie-Anne, Park John J, Lim Su Yin
Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, New South Wales, Australia.
Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia.
Int J Cancer. 2025 Sep 15;157(6):1031-1042. doi: 10.1002/ijc.35477. Epub 2025 May 14.
Soft tissue sarcoma (STS) is a rare and heterogeneous cancer, comprising approximately 1% of all adult cancers and 7%-15% of all childhood cancers. In the advanced stages, chemotherapy remains the standard-of-care, but efficacy is limited, with a response rate of 15%-30%, and responses are often short-lived, with median progression-free survival typically of 6 months. Moreover, patients with advanced or metastatic STS have a median overall survival of only 18-24 months. Immune checkpoint inhibitors (ICI) have revolutionized the treatment of various cancers including melanoma and non-small cell lung cancer (NSCLC). Emerging evidence from recent clinical trials indicates that certain STS subtypes may be amenable to immunotherapy. A critical challenge, however, is identifying biomarkers that can accurately predict and enable monitoring of ICI responses, to enable better patient selection and to improve outcomes. This narrative review highlights the current research gap in the treatment of STS patients with ICI therapy, particularly the absence of reliable blood-based biomarkers to predict ICI response. In this review, we examine current clinical trials investigating the efficacy of ICI therapy in patients with STS and summarise circulating immune-related prognostic biomarkers in STS, including haematological indices, peripheral blood mononuclear cells, circulating proteins and DNA, and evaluate their potential as predictive biomarkers for ICI therapy. We propose that these immune-associated molecules may serve as predictive biomarkers to differentiate and monitor ICI response, thus presenting opportunities for personalised treatment for patients with STS.
软组织肉瘤（STS）是一种罕见的异质性癌症，约占所有成人癌症的1%，占所有儿童癌症的7%-15%。在晚期，化疗仍然是标准治疗方法，但疗效有限，缓解率为15%-30%，且缓解往往是短暂的，无进展生存期的中位数通常为6个月。此外，晚期或转移性STS患者的总生存期中位数仅为18-24个月。免疫检查点抑制剂（ICI）彻底改变了包括黑色素瘤和非小细胞肺癌（NSCLC）在内的各种癌症的治疗方式。最近临床试验的新证据表明，某些STS亚型可能适合免疫治疗。然而，一个关键挑战是识别能够准确预测并监测ICI反应的生物标志物，以便更好地选择患者并改善治疗结果。这篇叙述性综述强调了在ICI治疗STS患者方面目前的研究差距，特别是缺乏可靠的血液生物标志物来预测ICI反应。在本综述中，我们研究了当前调查ICI治疗STS患者疗效的临床试验，并总结了STS中循环免疫相关的预后生物标志物，包括血液学指标、外周血单个核细胞、循环蛋白和DNA，并评估了它们作为ICI治疗预测生物标志物的潜力。我们提出，这些免疫相关分子可能作为预测生物标志物来区分和监测ICI反应，从而为STS患者提供个性化治疗的机会。
