TY - JOUR
T1 - Multiplex tissue imaging harmonization
T2 - A multicenter experience from CIMAC-CIDC immuno-oncology biomarkers network
AU - Akturk, Guray
AU - Parra, Edwin R.
AU - Gjini, Evisa
AU - Lako, Ana
AU - Jack Lee, J.
AU - Neuberg, Donna
AU - Zhang, Jiexin
AU - Yao, Shen
AU - Laface, Ilaria
AU - Rogic, Anita
AU - Chen, Pei Hsuan
AU - Sanchez-Espiridion, Beatriz
AU - Del Valle, Diane M.
AU - Moravec, Radim
AU - Kinders, Robert
AU - Hudgens, Courtney
AU - Wu, Catherine
AU - Wistuba, Ignacio I.
AU - Thurin, Magdalena
AU - Hewitt, Stephen M.
AU - Rodig, Scott
AU - Gnjatic, Sacha
AU - Tetzlaff, Michael T.
N1 - Publisher Copyright:
2021 The Authors; Published by the American Association for Cancer Research
PY - 2021/9/15
Y1 - 2021/9/15
N2 - Purpose: 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. Experimental Design: 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. Results: 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. Conclusions: 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.
AB - Purpose: 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. Experimental Design: 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. Results: 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. Conclusions: 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.
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U2 - 10.1158/1078-0432.CCR-21-2051
DO - 10.1158/1078-0432.CCR-21-2051
M3 - Article
C2 - 34253580
AN - SCOPUS:85114856852
SN - 1078-0432
VL - 27
SP - 5072
EP - 5073
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 18
ER -