全面分析 23 种肿瘤适应证中的成纤维细胞激活蛋白表达：癌症免疫疗法中生物标志物开发的见解。
Comprehensive analysis of fibroblast activation protein expression across 23 tumor indications: insights for biomarker development in cancer immunotherapies.
机构信息
Roche Pharma Research and Early Development, Oncology, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Roche Pharma Research and Early Development, Data and Analytics, Roche Translational & Clinical Research Center, F. Hoffmann-La Roche Ltd, Little Falls, NJ, United States.
出版信息
Front Immunol. 2024 Mar 15;15:1352615. doi: 10.3389/fimmu.2024.1352615. eCollection 2024.
INTRODUCTION
Fibroblast activation protein (FAP) is predominantly upregulated in various tumor microenvironments and scarcely expressed in normal tissues.
METHODS
We analyzed FAP across 1216 tissue samples covering 23 tumor types and 70 subtypes.
RESULTS
Elevated FAP levels were notable in breast, pancreatic, esophageal, and lung cancers. Using immunohistochemistry and RNAseq, a correlation between FAP gene and protein expression was found. Evaluating FAP's clinical significance, we assessed 29 cohorts from 12 clinical trials, including both mono and combination therapies with the PD-L1 inhibitor atezolizumab and chemotherapy. A trend links higher FAP expression to poorer prognosis, particularly in RCC, across both treatment arms. However, four cohorts showed improved survival with high FAP, while in four others, FAP had no apparent survival impact.
CONCLUSIONS
Our results emphasize FAP's multifaceted role in therapy response, suggesting its potential as a cancer immunotherapy biomarker.
简介
成纤维细胞激活蛋白（FAP）在各种肿瘤微环境中显著上调，而在正常组织中很少表达。
方法
我们分析了涵盖 23 种肿瘤类型和 70 种亚型的 1216 个组织样本中的 FAP。
结果
在乳腺癌、胰腺癌、食管癌和肺癌中，FAP 水平显著升高。通过免疫组织化学和 RNAseq 分析，发现 FAP 基因与蛋白表达之间存在相关性。评估 FAP 的临床意义时，我们评估了来自 12 项临床试验的 29 个队列，包括 PD-L1 抑制剂阿特珠单抗单药和联合化疗的治疗。在两个治疗组中，FAP 表达水平较高与预后较差呈趋势相关，尤其是在 RCC 中。然而，有四个队列显示高 FAP 可提高生存率，而在另外四个队列中，FAP 对生存率没有明显影响。
结论
我们的结果强调了 FAP 在治疗反应中的多方面作用，提示其作为癌症免疫治疗生物标志物的潜力。
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