Multiplex Tissue Imaging Harmonization: A Multicenter Experience from CIMAC-CIDC Immuno-Oncology Biomarkers Network.
Multiplex Tissue Imaging Harmonization: A Multicenter Experience from CIMAC-CIDC Immuno-Oncology Biomarkers Network.
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DOI：
10.1158/1078-0432.ccr-21-2051
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发表时间：
2021-09-15
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癌症免疫监测和分析中心-癌症免疫数据共享（CIMAC-CIDC）网络由NCI癌症登月计划支持，旨在使用最先进的技术为癌症免疫治疗的临床试验提供相关分析。这一举措的基础是实施多重IHC检测，以确定肿瘤内免疫浸润的组成和分布，以确定其作为生物标志物的潜在作用。一个关键的未回答的问题涉及这种测定的相对保真度，以可靠地量化跨不同平台的肿瘤相关免疫细胞。在其实验室中比较了三个CIMAC研究中心：（i）图像分析算法，（ii）图像采集平台，（iii）多重染色方案。采用了两种不同的高维方法：单一载玻片上的多重IHC连续染色（MICSSS）和多重免疫荧光（mIF）。为了消除可能影响测定性能的变量，我们完成了多步协调过程，首先使用独立方案比较测定性能，然后整合实验室特定方案，最后在一组独立组织中验证这种协调方法。最终验证步骤生成的数据显示，组织类型内和组织类型间各标志物的研究中心间斯皮尔曼相关系数（r）≥0.85，总体平均变异系数较低，≤0.1。我们的研究结果支持方案和平台的可重复性，以使用相似的组织标本提供稳健和可比的数据，并证实CIMAC-CIDC分析因此可以放心地用于与临床结局的统计学关联，这在很大程度上独立于不同研究中心的研究中心、抗体选择、方案和平台。
The Cancer Immune Monitoring and Analysis Centers – Cancer Immunologic Data Commons (CIMAC-CIDC) network supported by the NCI Cancer Moonshot initiative was established to provide correlative analyses for clinical trials in cancer immunotherapy, using state-of-the-art technology. Fundamental to this initiative is implementation of multiplex IHC assays to define the composition and distribution of immune infiltrates within tumors in the context of their potential role as biomarkers. A critical unanswered question involves the relative fidelity of such assays to reliably quantify tumor-associated immune cells across different platforms. Three CIMAC sites compared across their laboratories: (i) image analysis algorithms, (ii) image acquisition platforms, (iii) multiplex staining protocols. Two distinct high-dimensional approaches were employed: multiplexed IHC consecutive staining on single slide (MICSSS) and multiplexed immunofluorescence (mIF). To eliminate variables potentially impacting assay performance, we completed a multistep harmonization process, first comparing assay performance using independent protocols followed by the integration of laboratory-specific protocols and finally, validating this harmonized approach in an independent set of tissues. Data generated at the final validation step showed an intersite Spearman correlation coefficient (r) of ≥0.85 for each marker within and across tissue types, with an overall low average coefficient of variation ≤0.1. Our results support interchangeability of protocols and platforms to deliver robust, and comparable data using similar tissue specimens and confirm that CIMAC-CIDC analyses may therefore be used with confidence for statistical associations with clinical outcomes largely independent of site, antibody selection, protocol, and platform across different sites.