Targeted Mass Spectrometry Enables Multiplexed Quantification of Immunomodulatory Proteins in Clinical Biospecimens.
Targeted Mass Spectrometry Enables Multiplexed Quantification of Immunomodulatory Proteins in Clinical Biospecimens.
复制标题
DOI：
10.3389/fimmu.2021.765898
复制
发表时间：
2021
影响因子：
7.3
通讯作者：
Paulovich AG
中科院分区：
文献类型：
--
作者：
Whiteaker JR;Lundeen RA;Zhao L;Schoenherr RM;Burian A;Huang D;Voytovich U;Wang T;Kennedy JJ;Ivey RG;Lin C;Murillo OD;Lorentzen TD;Thiagarajan M;Colantonio S;Caceres TW;Roberts RR;Knotts JG;Reading JJ;Kaczmarczyk JA;Richardson CW;Garcia-Buntley SS;Bocik W;Hewitt SM;Murray KE;Do N;Brophy M;Wilz SW;Yu H;Ajjarapu S;Boja E;Hiltke T;Rodriguez H;Paulovich AG
免疫疗法正在彻底改变癌症治疗，在一小部分患者中产生持久的反应并有可能治愈。然而，大多数肿瘤的反应率很低，3/4级毒性并不罕见，我们目前对肿瘤免疫生物学的了解尚不完整。虽然肿瘤微环境中有数百种免疫调节蛋白形成抗肿瘤反应，但它们中很少能被可靠地量化。为了满足这一需求，我们利用多肽免疫亲和富集和多重反应监测-质谱技术，开发了一种针对52个肽的靶向蛋白质组学分析，这些肽代表46种蛋白质。我们在组织和血浆基质中验证了该检测方法，其性能数据显示动态范围超过3个数量级，中间日cv为5.2%（组织）和21%（血浆）。临床生物标本的可行性研究表明，冷冻组织中可检测48/52肽，血浆中可检测38/52肽。这些检测作为一种资源公开提供给研究界。
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.
影响因子：
9.3
作者：
Schoenherr RM;Voytovich UJ;Whiteaker JR;Gadi VK;Gralow JR;Paulovich AG
通讯作者：
Paulovich AG