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Targeted Mass Spectrometry Enables Multiplexed Quantification of Immunomodulatory Proteins in Clinical Biospecimens

2021; Frontiers Media; Volume: 12; Linguagem: Inglês

10.3389/fimmu.2021.765898

1664-3224

Jeffrey R. Whiteaker, Rachel A. Lundeen, Lei Zhao, Regine M. Schoenherr, Aura Burian, Dongqing Huang, Ulianna Voytovich, Tao Wang, Jacob J. Kennedy, Richard G. Ivey, Chenwei Lin, Oscar Murillo, Travis D. Lorentzen, Mathangi Thiagarajan, Simona Colantonio, Tessa W. Caceres, Rhonda R. Roberts, Joseph G. Knotts, Joshua J. Reading, Jan Kaczmarczyk, Christopher W. Richardson, Sandra S. Garcia-Buntley, William Bocik, Stephen M. Hewitt, Karen Murray, Nhan Do, Mary T. Brophy, Stephen W. Wilz, Hongbo Yu, Samuel Ajjarapu, Emily S. Boja, Tara Hiltke, Henry Rodriguez, Amanda G. Paulovich,

Advanced biosensing and bioanalysis techniques

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.