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

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 im...

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Autores principales:	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, Mary Brophy, Stephen W. Wilz, Hongbo Yu, Samuel Ajjarapu, Emily Boja, Tara Hiltke, Henry Rodriguez, Amanda G. Paulovich
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	immunotherapy cancer correlative biomarkers mass spectrometry immuno-MRM Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/2231b7f4bf4c4dfdac9a7d21bf8f78b2
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spelling	oai:doaj.org-article:2231b7f4bf4c4dfdac9a7d21bf8f78b22021-11-11T08:45:18ZTargeted Mass Spectrometry Enables Multiplexed Quantification of Immunomodulatory Proteins in Clinical Biospecimens1664-322410.3389/fimmu.2021.765898https://doaj.org/article/2231b7f4bf4c4dfdac9a7d21bf8f78b22021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.765898/fullhttps://doaj.org/toc/1664-3224Immunotherapies 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.Jeffrey R. WhiteakerRachel A. LundeenLei ZhaoRegine M. SchoenherrAura BurianDongqing HuangUlianna VoytovichTao WangJacob J. KennedyRichard G. IveyChenwei LinOscar D. MurilloTravis D. LorentzenMathangi ThiagarajanSimona ColantonioTessa W. CaceresRhonda R. RobertsJoseph G. KnottsJoshua J. ReadingJan A. KaczmarczykChristopher W. RichardsonSandra S. Garcia-BuntleyWilliam BocikStephen M. HewittKaren E. MurrayNhan DoNhan DoMary BrophyMary BrophyStephen W. WilzStephen W. WilzHongbo YuHongbo YuSamuel AjjarapuSamuel AjjarapuEmily BojaTara HiltkeHenry RodriguezAmanda G. PaulovichFrontiers Media S.A.articleimmunotherapycancercorrelative biomarkersmass spectrometryimmuno-MRMImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	immunotherapy cancer correlative biomarkers mass spectrometry immuno-MRM Immunologic diseases. Allergy RC581-607
spellingShingle	immunotherapy cancer correlative biomarkers mass spectrometry immuno-MRM Immunologic diseases. Allergy RC581-607 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 Targeted Mass Spectrometry Enables Multiplexed Quantification of Immunomodulatory Proteins in Clinical Biospecimens
description	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.
format	article
author	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
author_facet	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
author_sort	Jeffrey R. Whiteaker
title	Targeted Mass Spectrometry Enables Multiplexed Quantification of Immunomodulatory Proteins in Clinical Biospecimens
title_short	Targeted Mass Spectrometry Enables Multiplexed Quantification of Immunomodulatory Proteins in Clinical Biospecimens
title_full	Targeted Mass Spectrometry Enables Multiplexed Quantification of Immunomodulatory Proteins in Clinical Biospecimens
title_fullStr	Targeted Mass Spectrometry Enables Multiplexed Quantification of Immunomodulatory Proteins in Clinical Biospecimens
title_full_unstemmed	Targeted Mass Spectrometry Enables Multiplexed Quantification of Immunomodulatory Proteins in Clinical Biospecimens
title_sort	targeted mass spectrometry enables multiplexed quantification of immunomodulatory proteins in clinical biospecimens
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/2231b7f4bf4c4dfdac9a7d21bf8f78b2
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Targeted Mass Spectrometry Enables Multiplexed Quantification of Immunomodulatory Proteins in Clinical Biospecimens

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