肉瘤免疫检查点抑制的生物标志物 - 我们离临床应用近了吗?
Biomarkers for immune checkpoint inhibition in sarcomas - are we close to clinical implementation?
发表日期:2023 Aug 23
作者:
Chin Sern Yiong, Tzu Ping Lin, Vivian Yujing Lim, Tan Boon Toh, Valerie Shiwen Yang
来源:
Cellular & Molecular Immunology
摘要:
肉瘤是一组多样且复杂的由间叶起源的癌症,相关理解尚不完全。癌症免疫治疗的最新进展表明,在某些肉瘤中,与传统化疗相比,通过免疫检查点抑制可能获得更好的结果。免疫检查点抑制剂(ICIs)是癌症免疫治疗的关键药物,在许多肿瘤类型中表现出改善的治疗效果。然而,大多数肉瘤患者并未从治疗中受益,这突显了用于ICIs反应预测生物标志物的鉴定和开发的需求。在本综述中,我们首先讨论了美国食品药品监督管理局(FDA)和欧洲药品管理局(EMA)批准的生物标志物以及其在肉瘤中使用的限制。然后,我们回顾了八个潜在的预测性生物标志物,并对其在肉瘤中的实用性进行了合理化说明。这些标志物包括基因表达特征(GES)、循环中性粒细胞与淋巴细胞比值(NLR)、吲哚胺2,3-二氧化酶(IDO)、淋巴细胞活化基因3(LAG-3)、T细胞免疫球蛋白和黏蛋白结构域蛋白3(TIM-3)、TP53突变状态、B细胞和三级淋巴结构(TLS)。最后,我们讨论了TLS作为ICIs对肉瘤反应的预测和预后生物标志物,在临床上的潜力和实施情况。©2023 Yumed Inc. 和BioMed Central Ltd., 属于Springer Nature。
Sarcomas are a group of diverse and complex cancers of mesenchymal origin that remains poorly understood. Recent developments in cancer immunotherapy have demonstrated a potential for better outcomes with immune checkpoint inhibition in some sarcomas compared to conventional chemotherapy. Immune checkpoint inhibitors (ICIs) are key agents in cancer immunotherapy, demonstrating improved outcomes in many tumor types. However, most patients with sarcoma do not benefit from treatment, highlighting the need for identification and development of predictive biomarkers for response to ICIs. In this review, we first discuss United States (US) Food and Drug Administration (FDA)-approved and European Medicines Agency (EMA)-approved biomarkers, as well as the limitations of their use in sarcomas. We then review eight potential predictive biomarkers and rationalize their utility in sarcomas. These include gene expression signatures (GES), circulating neutrophil-to-lymphocyte ratio (NLR), indoleamine 2,3-dioxygenase (IDO), lymphocyte activation gene 3 (LAG-3), T cell immunoglobin and mucin domain-containing protein 3 (TIM-3), TP53 mutation status, B cells, and tertiary lymphoid structures (TLS). Finally, we discuss the potential for TLS as both a predictive and prognostic biomarker for ICI response in sarcomas to be implemented in the clinic.© 2023. Yumed Inc. and BioMed Central Ltd., part of Springer Nature.