Immune profiling mass cytometry assay harmonization: Multicenter experience from CIMAC-CIDC

Bita Sahaf, Mina Pichavant, Brian H. Lee, Caroline Duault, Emily M. Thrash, Melanie Davila, Nicolas Fernandez, Karen Millerchip, Salah Eddine Bentebibel, Cara Haymaker, Natalia Sigal, Diane M. Del Valle, Srinika Ranasinghe, Sarah Fayle, Beatriz Sanchez-Espiridion, Jiexin Zhang, Chantale Bernatchez, Catherine J. Wu, Ignacio I. Wistuba, Seunghee Kim-SchulzeSacha Gnjatic, Sean C. Bendall, Minkyung Song, Magdalena Thurin, J. Jack Lee, Holden T. Maecker, Adeeb Rahman

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)5062-5072
Number of pages11
JournalClinical Cancer Research
Volume27
Issue number18
DOIs
StatePublished - Sep 15 2021

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

MD Anderson CCSG core facilities

  • Bioinformatics Shared Resource
  • Biostatistics Resource Group

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