TY - JOUR
T1 - Immune profiling mass cytometry assay harmonization
T2 - Multicenter experience from CIMAC-CIDC
AU - Sahaf, Bita
AU - Pichavant, Mina
AU - Lee, Brian H.
AU - Duault, Caroline
AU - Thrash, Emily M.
AU - Davila, Melanie
AU - Fernandez, Nicolas
AU - Millerchip, Karen
AU - Bentebibel, Salah Eddine
AU - Haymaker, Cara
AU - Sigal, Natalia
AU - Del Valle, Diane M.
AU - Ranasinghe, Srinika
AU - Fayle, Sarah
AU - Sanchez-Espiridion, Beatriz
AU - Zhang, Jiexin
AU - Bernatchez, Chantale
AU - Wu, Catherine J.
AU - Wistuba, Ignacio I.
AU - Kim-Schulze, Seunghee
AU - Gnjatic, Sacha
AU - Bendall, Sean C.
AU - Song, Minkyung
AU - Thurin, Magdalena
AU - Jack Lee, J.
AU - Maecker, Holden T.
AU - Rahman, Adeeb
N1 - Funding Information:
E.M. Thrash reports personal fees from Fluidigm Corporation during the conduct of the study and personal fees from Fluidigm Corporation outside the submitted work; in addition, E.M. Thrash is an employee at Current Fluidigm. N. Fernandez reports personal fees from Vizgen outside the submitted work. C. Haymaker reports personal fees from Briacell Therapeutics outside the submitted work. C. Bernatchez reports grants from NCI during the conduct of the study and other support from Myst Therapeutics outside the submitted work. C.J. Wu reports other support from Pharmacyclics outside the submitted work. I.I. Wistuba reports grants and personal fees from Genentech/Roche, Bayer, AstraZeneca, Pfizer, HTG Molecular, Merck, Guardant Health, and Novartis; personal fees from Bristol Myers Squibb, GlaxoSmithKline, Oncocyte, and MSD; grants from Adaptive, Adaptimmune, EMD Serono, Takeda, Amgen, Karus, Johnson & Johnson, Iovance, 4D, and Lilly; and grants from Akoya outside the submitted work. S. Gnjatic reports grants from Regeneron, BMS, Takeda, Genentech, and Janssen R&D; personal fees from OncoMed; and personal fees from Merck outside the submitted work. S.C. Bendall reports personal fees from Ionpath, and Purigen and grants from Biogen outside the submitted work. H.T. Maecker reports grants from NIH during the conduct of the study. A. Rahman reports grants from NIH/NCI during the conduct of the study; in addition, A. Rahman has a patent for metal-labeled reference standards for mass cytometry licensed to Biolegend. No disclosures were reported by the other authors.
Funding Information:
Scientific and financial support for the CIMAC-CIDC Network are provided through the NCI Cooperative Agreements U24CA224319 (to the Icahn School of Medicine at Mount Sinai CIMAC), U24CA224331 (to the Dana-Farber Cancer Institute CIMAC), U24CA224285 (to the University of Texas MD Anderson Cancer Center CIMAC), U24CA224309 (to the Stanford University CIMAC), and U24CA224316 (to the CIDC at Dana-Farber Cancer Institute). Additional support is made possible through the NCI CTIMS Contract HHSN261201600002C (to the Emmes Company, LLC). MDACC received support from NIH Cancer Center Support Grant P30CA016672 and the University of Texas SPORE NCI P50CA70907. Scientific and financial support for the PACT project are made possible through funding support provided to the FNIH by AbbVie Inc., Amgen Inc., Boehringer-
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 is supported by the NCI to identify biomarkers of response to cancer immunotherapies across clinical trials using state-of-the-art assays. A primary platform for CIMAC-CIDC studies is cytometry by time of flight (CyTOF), performed at all CIMAC laboratories. To ensure the ability to generate comparable CyTOF data across labs, a multistep cross-site harmonization effort was undertaken. Experimental Design: We first harmonized standard operating procedures (SOPs) across the CIMAC sites. Because of a new acquisition protocol comparing original narrow- or new wide-bore injector introduced by the vendor (Fluidigm), we also tested this protocol across sites before finalizing the harmonized SOP. We then performed cross-site assay harmonization experiments using five shared cryopreserved and one lyophilized internal control peripheral blood mononuclear cell (PBMC) with a shared lyophilized antibody cocktail consisting of 14 isotype-tagged antibodies previously validated, plus additional liquid antibodies. These reagents and samples were distributed to the CIMAC sites and the data were centrally analyzed by manual gating and automated methods (Astrolabe). Results: Average coefficients of variation (CV) across sites for each cell population were reported and compared with a previous multisite CyTOF study. We reached an intersite CV of under 20% for most cell subsets, very similar to a previously published study. Conclusions: These results establish the ability to reproduce CyTOF data across sites in multicenter clinical trials, and also highlight the importance of quality control procedures, such as the use of spike-in control samples, for tracking variability in this assay.
AB - Purpose: The Cancer Immune Monitoring and Analysis Centers – Cancer Immunologic Data Commons (CIMAC-CIDC) Network is supported by the NCI to identify biomarkers of response to cancer immunotherapies across clinical trials using state-of-the-art assays. A primary platform for CIMAC-CIDC studies is cytometry by time of flight (CyTOF), performed at all CIMAC laboratories. To ensure the ability to generate comparable CyTOF data across labs, a multistep cross-site harmonization effort was undertaken. Experimental Design: We first harmonized standard operating procedures (SOPs) across the CIMAC sites. Because of a new acquisition protocol comparing original narrow- or new wide-bore injector introduced by the vendor (Fluidigm), we also tested this protocol across sites before finalizing the harmonized SOP. We then performed cross-site assay harmonization experiments using five shared cryopreserved and one lyophilized internal control peripheral blood mononuclear cell (PBMC) with a shared lyophilized antibody cocktail consisting of 14 isotype-tagged antibodies previously validated, plus additional liquid antibodies. These reagents and samples were distributed to the CIMAC sites and the data were centrally analyzed by manual gating and automated methods (Astrolabe). Results: Average coefficients of variation (CV) across sites for each cell population were reported and compared with a previous multisite CyTOF study. We reached an intersite CV of under 20% for most cell subsets, very similar to a previously published study. Conclusions: These results establish the ability to reproduce CyTOF data across sites in multicenter clinical trials, and also highlight the importance of quality control procedures, such as the use of spike-in control samples, for tracking variability in this assay.
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U2 - 10.1158/1078-0432.CCR-21-2052
DO - 10.1158/1078-0432.CCR-21-2052
M3 - Article
C2 - 34266889
AN - SCOPUS:85115020105
SN - 1078-0432
VL - 27
SP - 5062
EP - 5072
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 18
ER -