{"title":"CD34 作为晚期非小细胞肺癌康瑞珠单抗反应的潜在预后指标：数字空间图谱分析的启示。","authors":"Xinyi Huang, Baoqing Tian, Ziyuan Ren, Jingxin Zhang, Weiwei Yan, You Mo, Jupeng Yuan, Yujiao Ma, Ruiyang Wang, Rufei Liu, Minxin Chen, Jinming Yu, Dawei Chen","doi":"10.1177/17588359241289671","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Given that only a small subset of patients with advanced non-small-cell lung cancer (aNSCLC) benefit from immune checkpoint inhibitors (ICIs), the effectiveness of ICIs is often compromised by the complex interplay within the tumor microenvironment (TME).</p><p><strong>Objectives: </strong>To identify predictive biomarkers associated with ICI resistance at a multi-omics spatial level.</p><p><strong>Design: </strong>A total of eight aNSCLC patients who received first-line anti-programmed cell death protein-1 (PD-1) monoclonal antibody camrelizumab at Shandong Cancer Hospital and Institute between 2021 and 2022 were included in the discovery cohort. An additional validation cohort of 45 samples from camrelizumab-treated aNSCLC patients was also enrolled.</p><p><strong>Methods: </strong>NanoString GeoMx<sup>®</sup> digital spatial profiling was conducted at the transcriptomic and proteomic level within pan-cytokeratin (panCK<sup>+</sup>), CD45<sup>+</sup>, and CD68<sup>+</sup> compartments. For validation, multiplex immunofluorescence (mIF) staining was performed.</p><p><strong>Results: </strong>Distinct spatial expression patterns and levels of immune infiltration were observed between tumor and leukocyte compartments. Higher CD34 expression in the macrophage compartment correlated with poorer prognosis and response to camrelizumab (<i>p</i> < 0.05). mIF validation confirmed the association of elevated CD34 expression level with reduced progression-free survival (PFS; hazard ratio (HR) = 5.011, 95% confidence interval: 1.057-23.752, <i>p</i> = 0.042), outperforming traditional tumor markers in predictive accuracy.</p><p><strong>Conclusion: </strong>Our findings identify CD34 as a novel spatial biomarker for anti-PD-1 therapy efficacy, potentially guiding the selection of aNSCLC patients who are more likely to benefit from ICI treatment.</p><p><strong>Trial registration: </strong>ChiCTR2000040416.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"16 ","pages":"17588359241289671"},"PeriodicalIF":4.3000,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11489950/pdf/","citationCount":"0","resultStr":"{\"title\":\"CD34 as a potential prognostic indicator for camrelizumab response in advanced non-small-cell lung cancer: insights from digital spatial profiling.\",\"authors\":\"Xinyi Huang, Baoqing Tian, Ziyuan Ren, Jingxin Zhang, Weiwei Yan, You Mo, Jupeng Yuan, Yujiao Ma, Ruiyang Wang, Rufei Liu, Minxin Chen, Jinming Yu, Dawei Chen\",\"doi\":\"10.1177/17588359241289671\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Given that only a small subset of patients with advanced non-small-cell lung cancer (aNSCLC) benefit from immune checkpoint inhibitors (ICIs), the effectiveness of ICIs is often compromised by the complex interplay within the tumor microenvironment (TME).</p><p><strong>Objectives: </strong>To identify predictive biomarkers associated with ICI resistance at a multi-omics spatial level.</p><p><strong>Design: </strong>A total of eight aNSCLC patients who received first-line anti-programmed cell death protein-1 (PD-1) monoclonal antibody camrelizumab at Shandong Cancer Hospital and Institute between 2021 and 2022 were included in the discovery cohort. An additional validation cohort of 45 samples from camrelizumab-treated aNSCLC patients was also enrolled.</p><p><strong>Methods: </strong>NanoString GeoMx<sup>®</sup> digital spatial profiling was conducted at the transcriptomic and proteomic level within pan-cytokeratin (panCK<sup>+</sup>), CD45<sup>+</sup>, and CD68<sup>+</sup> compartments. For validation, multiplex immunofluorescence (mIF) staining was performed.</p><p><strong>Results: </strong>Distinct spatial expression patterns and levels of immune infiltration were observed between tumor and leukocyte compartments. Higher CD34 expression in the macrophage compartment correlated with poorer prognosis and response to camrelizumab (<i>p</i> < 0.05). mIF validation confirmed the association of elevated CD34 expression level with reduced progression-free survival (PFS; hazard ratio (HR) = 5.011, 95% confidence interval: 1.057-23.752, <i>p</i> = 0.042), outperforming traditional tumor markers in predictive accuracy.</p><p><strong>Conclusion: </strong>Our findings identify CD34 as a novel spatial biomarker for anti-PD-1 therapy efficacy, potentially guiding the selection of aNSCLC patients who are more likely to benefit from ICI treatment.</p><p><strong>Trial registration: </strong>ChiCTR2000040416.</p>\",\"PeriodicalId\":23053,\"journal\":{\"name\":\"Therapeutic Advances in Medical Oncology\",\"volume\":\"16 \",\"pages\":\"17588359241289671\"},\"PeriodicalIF\":4.3000,\"publicationDate\":\"2024-10-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11489950/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Therapeutic Advances in Medical Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1177/17588359241289671\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Therapeutic Advances in Medical Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/17588359241289671","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
背景：鉴于只有一小部分晚期非小细胞肺癌（aNSCLC）患者从免疫检查点抑制剂（ICIs）中获益，ICIs的有效性往往会受到肿瘤微环境（TME）内复杂相互作用的影响：在多组学空间水平上确定与 ICI 耐药性相关的预测性生物标志物：设计：发现队列中纳入了2021年至2022年期间在山东省肿瘤医院和研究所接受一线抗程序性细胞死亡蛋白-1（PD-1）单克隆抗体康瑞珠单抗治疗的8例ANSCLC患者。另外还加入了一个验证队列，该队列中有45个样本来自接受过康瑞珠单抗治疗的非小细胞肺癌患者：方法：在泛细胞角蛋白（panCK+）、CD45+和CD68+区段内进行了转录组和蛋白质组水平的NanoString GeoMx®数字空间谱分析。为了进行验证，还进行了多重免疫荧光（mIF）染色：结果：在肿瘤和白细胞间观察到了不同的空间表达模式和免疫浸润水平。巨噬细胞分区中 CD34 的高表达与较差的预后和对坎瑞珠单抗的反应相关（p p = 0.042），其预测准确性优于传统的肿瘤标志物：我们的研究结果表明，CD34是抗PD-1疗法疗效的新型空间生物标志物，可能指导选择更有可能从ICI治疗中获益的非小细胞肺癌患者：ChiCTR2000040416。
CD34 as a potential prognostic indicator for camrelizumab response in advanced non-small-cell lung cancer: insights from digital spatial profiling.
Background: Given that only a small subset of patients with advanced non-small-cell lung cancer (aNSCLC) benefit from immune checkpoint inhibitors (ICIs), the effectiveness of ICIs is often compromised by the complex interplay within the tumor microenvironment (TME).
Objectives: To identify predictive biomarkers associated with ICI resistance at a multi-omics spatial level.
Design: A total of eight aNSCLC patients who received first-line anti-programmed cell death protein-1 (PD-1) monoclonal antibody camrelizumab at Shandong Cancer Hospital and Institute between 2021 and 2022 were included in the discovery cohort. An additional validation cohort of 45 samples from camrelizumab-treated aNSCLC patients was also enrolled.
Methods: NanoString GeoMx® digital spatial profiling was conducted at the transcriptomic and proteomic level within pan-cytokeratin (panCK+), CD45+, and CD68+ compartments. For validation, multiplex immunofluorescence (mIF) staining was performed.
Results: Distinct spatial expression patterns and levels of immune infiltration were observed between tumor and leukocyte compartments. Higher CD34 expression in the macrophage compartment correlated with poorer prognosis and response to camrelizumab (p < 0.05). mIF validation confirmed the association of elevated CD34 expression level with reduced progression-free survival (PFS; hazard ratio (HR) = 5.011, 95% confidence interval: 1.057-23.752, p = 0.042), outperforming traditional tumor markers in predictive accuracy.
Conclusion: Our findings identify CD34 as a novel spatial biomarker for anti-PD-1 therapy efficacy, potentially guiding the selection of aNSCLC patients who are more likely to benefit from ICI treatment.
期刊介绍：
Therapeutic Advances in Medical Oncology is an open access, peer-reviewed journal delivering the highest quality articles, reviews, and scholarly comment on pioneering efforts and innovative studies in the medical treatment of cancer. The journal has a strong clinical and pharmacological focus and is aimed at clinicians and researchers in medical oncology, providing a forum in print and online for publishing the highest quality articles in this area. This journal is a member of the Committee on Publication Ethics (COPE).
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