Multiplex Tissue Imaging Harmonization: A Multicenter Experience from CIMAC-CIDC Immuno-Oncology Biomarkers Network.
IF: 13.801
Cited by: 8


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.



MeSH terms

Biomarkers, Tumor
Fluorescent Antibody Technique
Image Processing, Computer-Assisted
Monitoring, Immunologic
Staining and Labeling


Akturk, Guray
Parra, Edwin R
Gjini, Evisa
Lako, Ana
Lee, J Jack
Neuberg, Donna
Zhang, Jiexin
Yao, Shen
Laface, Ilaria
Rogic, Anita
Chen, Pei-Hsuan
Sanchez-Espiridion, Beatriz
Valle, Diane M Del
Moravec, Radim
Kinders, Robert
Hudgens, Courtney
Wu, Catherine
Wistuba, Ignacio I
Thurin, Magdalena
Hewitt, Stephen M
Rodig, Scott
Gnjatic, Sacha
Tetzlaff, Michael T

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