[表达 PD-L1 的癌症相关成纤维细胞有望成为免疫检查点抑制剂的生物标记物]

Q4 Medicine Japanese Journal of Cancer and Chemotherapy Pub Date : 2024-09-01
Kento Kawasaki, Kazuhiro Noma, Toshiyoshi Fujiwara
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引用次数: 0

摘要

众所周知,程序性细胞死亡1(PD-1)/程序性细胞死亡配体1(PD-L1)轴是抑制免疫反应和促进自身耐受的系统。包括 PD-1/PD-L1 轴在内的免疫检查点抑制剂(ICIs)的临床适应症正在急剧扩大。然而,由于 ICIs 对某些类型的癌症无效或产生耐药性,因此有望开发出更有效的联合疗法或疗效预测指标和生物标志物。另一方面,我们一直在关注作为治疗靶点的肿瘤微环境(TME),并一直在分析在肿瘤微环境中发挥核心作用的癌症相关成纤维细胞(CAFs)的功能。最近,CAFs 被认为会诱导肿瘤进入免疫抑制状态,这表明 ICIs 在这样的癌症微环境中可能无效。在这篇综述中,我们通过免疫组化方法证明了切除标本中癌细胞和 CAFs 中 PD-L1 阳性的影响。此外,我们还评估了 PD-L1 阳性 CAFs 作为 ICIs 治疗靶点和生物标记物的潜力。
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[PD-L1-Expressing Cancer-Associated Fibroblasts Have the Potential of a Biomarker for Immune Checkpoint Inhibitors].

Programmed cell death 1(PD-1)/programmed cell death ligand 1(PD-L1)axis is well known as the system resulting in the inhibition of immune responses and promotion of self-tolerance. The clinical indications for immune checkpoint inhibitors( ICIs), including the targeting of PD-1/PD-L1 axis, are dramatically expanding. However, since ICIs have been found to be ineffective or resistant in some types of cancer, the development of more effective combination therapies or predictors and biomarkers of efficacy are expected. On the other hand, we have been focusing on the tumor microenvironment(TME)as a therapeutic target, and have been analyzing the function of cancer-associated fibroblasts(CAFs), which play a central role in TME. Recently, CAFs are known to induce tumors to an immunosuppressive state, suggesting that ICIs may not be effective in such a cancer microenvironment. In this review, we demonstrated the impact of PD-L1 positivity in cancer cells and CAFs by immunohistochemistry for resected specimens. In addition, we evaluated the potential of PD-L1-positve CAFs for therapeutic target and biomarker for ICIs.

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