Targeted Mass Spectrometry Enables Multiplexed Quantification of Immunomodulatory Proteins in Clinical Biospecimens
| Autor: | Rhonda R. Roberts, Christopher W. Richardson, Aura Burian, Lei Zhao, Karen E. Murray, Regine M. Schoenherr, Amanda G. Paulovich, Sandra S. Garcia-Buntley, Jan Kaczmarczyk, Oscar Murillo, Mathangi Thiagarajan, Richard G. Ivey, Emily S. Boja, Rachel A. Lundeen, Samuel Ajjarapu, Ulianna Voytovich, Hongbo Yu, Chenwei Lin, Tessa W. Caceres, Jacob J. Kennedy, William Bocik, Tara Hiltke, Joshua J. Reading, Henry Rodriguez, Stephen M. Hewitt, Nhan Do, Stephen W. Wilz, Dongqing Huang, Simona Colantonio, Mary Brophy, Jeffrey R. Whiteaker, Joseph G. Knotts, Travis D. Lorentzen, Tao Wang |
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| Rok vydání: | 2021 |
| Předmět: |
Proteomics
Proteome medicine.medical_treatment Blotting Western Immunology Peptide Computational biology Antibodies Mass Spectrometry Specimen Handling Jurkat Cells correlative biomarkers Research community Cell Line Tumor Methods Medicine Immunology and Allergy Humans cancer Multiplex RNA-Seq Frozen tissue chemistry.chemical_classification Tumor microenvironment business.industry Cancer Reproducibility of Results Immunotherapy RC581-607 medicine.disease immuno-MRM Targeted mass spectrometry chemistry MCF-7 Cells immunotherapy Immunologic diseases. Allergy business Peptides Chromatography Liquid HeLa Cells |
| Zdroj: | Frontiers in Immunology Frontiers in Immunology, Vol 12 (2021) |
| ISSN: | 1664-3224 |
| Popis: | Immunotherapies are revolutionizing cancer care, producing durable responses and potentially cures in a subset of patients. However, response rates are low for most tumors, grade 3/4 toxicities are not uncommon, and our current understanding of tumor immunobiology is incomplete. While hundreds of immunomodulatory proteins in the tumor microenvironment shape the anti-tumor response, few of them can be reliably quantified. To address this need, we developed a multiplex panel of targeted proteomic assays targeting 52 peptides representing 46 proteins using peptide immunoaffinity enrichment coupled to multiple reaction monitoring-mass spectrometry. We validated the assays in tissue and plasma matrices, where performance figures of merit showed over 3 orders of dynamic range and median inter-day CVs of 5.2% (tissue) and 21% (plasma). A feasibility study in clinical biospecimens showed detection of 48/52 peptides in frozen tissue and 38/52 peptides in plasma. The assays are publicly available as a resource for the research community. |
| Databáze: | OpenAIRE |
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