Frontiers in Immunology (Nov 2021)
Targeted Mass Spectrometry Enables Multiplexed Quantification of Immunomodulatory Proteins in Clinical Biospecimens
- 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 D. Murillo,
- Travis D. Lorentzen,
- Mathangi Thiagarajan,
- Simona Colantonio,
- Tessa W. Caceres,
- Rhonda R. Roberts,
- Joseph G. Knotts,
- Joshua J. Reading,
- Jan A. Kaczmarczyk,
- Christopher W. Richardson,
- Sandra S. Garcia-Buntley,
- William Bocik,
- Stephen M. Hewitt,
- Karen E. Murray,
- Nhan Do,
- Nhan Do,
- Mary Brophy,
- Mary Brophy,
- Stephen W. Wilz,
- Stephen W. Wilz,
- Hongbo Yu,
- Hongbo Yu,
- Samuel Ajjarapu,
- Samuel Ajjarapu,
- Emily Boja,
- Tara Hiltke,
- Henry Rodriguez,
- Amanda G. Paulovich
Affiliations
- Jeffrey R. Whiteaker
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States
- Rachel A. Lundeen
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States
- Lei Zhao
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States
- Regine M. Schoenherr
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States
- Aura Burian
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States
- Dongqing Huang
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States
- Ulianna Voytovich
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States
- Tao Wang
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States
- Jacob J. Kennedy
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States
- Richard G. Ivey
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States
- Chenwei Lin
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States
- Oscar D. Murillo
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States
- Travis D. Lorentzen
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States
- Mathangi Thiagarajan
- Frederick National Laboratory for Cancer Research, Frederick, MD, United States
- Simona Colantonio
- Cancer Research Technology Program, Antibody Characterization Lab, Frederick National Laboratory for Cancer Research, Frederick, MD, United States
- Tessa W. Caceres
- Cancer Research Technology Program, Antibody Characterization Lab, Frederick National Laboratory for Cancer Research, Frederick, MD, United States
- Rhonda R. Roberts
- Cancer Research Technology Program, Antibody Characterization Lab, Frederick National Laboratory for Cancer Research, Frederick, MD, United States
- Joseph G. Knotts
- Cancer Research Technology Program, Antibody Characterization Lab, Frederick National Laboratory for Cancer Research, Frederick, MD, United States
- Joshua J. Reading
- Cancer Research Technology Program, Antibody Characterization Lab, Frederick National Laboratory for Cancer Research, Frederick, MD, United States
- Jan A. Kaczmarczyk
- Cancer Research Technology Program, Antibody Characterization Lab, Frederick National Laboratory for Cancer Research, Frederick, MD, United States
- Christopher W. Richardson
- Cancer Research Technology Program, Antibody Characterization Lab, Frederick National Laboratory for Cancer Research, Frederick, MD, United States
- Sandra S. Garcia-Buntley
- Cancer Research Technology Program, Antibody Characterization Lab, Frederick National Laboratory for Cancer Research, Frederick, MD, United States
- William Bocik
- Cancer Research Technology Program, Antibody Characterization Lab, Frederick National Laboratory for Cancer Research, Frederick, MD, United States
- Stephen M. Hewitt
- Experimental Pathology Laboratory, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institute of Health, Bethesda, MD, United States
- Karen E. Murray
- Veteran’s Administration (VA) Cooperative Studies Program, Veteran’s Administration (VA) Boston Healthcare System (151MAV), Jamaica Plain, MA, United States
- Nhan Do
- Veteran’s Administration (VA) Cooperative Studies Program, Veteran’s Administration (VA) Boston Healthcare System (151MAV), Jamaica Plain, MA, United States
- Nhan Do
- Department of Medicine, Boston University School of Medicine, Boston, MA, United States
- Mary Brophy
- Veteran’s Administration (VA) Cooperative Studies Program, Veteran’s Administration (VA) Boston Healthcare System (151MAV), Jamaica Plain, MA, United States
- Mary Brophy
- Department of Medicine, Boston University School of Medicine, Boston, MA, United States
- Stephen W. Wilz
- Department of Medicine, Boston University School of Medicine, Boston, MA, United States
- Stephen W. Wilz
- Pathology and Laboratory Medicine Service, Program, Veteran’s Administration (VA) Boston Healthcare System, Jamaica Plain, MA, United States
- Hongbo Yu
- Pathology and Laboratory Medicine Service, Program, Veteran’s Administration (VA) Boston Healthcare System, Jamaica Plain, MA, United States
- Hongbo Yu
- Department of Pathology, Harvard Medical School, Boston, MA, United States
- Samuel Ajjarapu
- Veteran’s Administration (VA) Cooperative Studies Program, Veteran’s Administration (VA) Boston Healthcare System (151MAV), Jamaica Plain, MA, United States
- Samuel Ajjarapu
- Department of Medicine, Dana-Farber Cancer Institute, Boston, MA, United States
- Emily Boja
- 0Office of Cancer Clinical Proteomics Research, National Cancer Institute, Bethesda, MD, United States
- Tara Hiltke
- 0Office of Cancer Clinical Proteomics Research, National Cancer Institute, Bethesda, MD, United States
- Henry Rodriguez
- 0Office of Cancer Clinical Proteomics Research, National Cancer Institute, Bethesda, MD, United States
- Amanda G. Paulovich
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States
- DOI
- https://doi.org/10.3389/fimmu.2021.765898
- Journal volume & issue
-
Vol. 12
Abstract
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.
Keywords
