Journal
FRONTIERS IN IMMUNOLOGY
Volume 12, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2021.765898
Keywords
immunotherapy; cancer; correlative biomarkers; mass spectrometry; immuno-MRM
Categories
Funding
- National Cancer Institute (NCI)
- National Institutes of Health
- NCI Beau Biden National Cancer Moonshot [HHSN26100025]
- NCI Clinical Proteomics Tumor Analysis Consortium (CPTAC) [U01CA214114]
- Applied Proteogenomics Organizational Learning and Outcomes [HHSN261201500003I]
- NCI Research Specialist program [R50CA211499]
- NCI CPTAC Antibody Characterization Program
- Aven Foundation
- VA Office of Research and Development, Cooperative Studies Program (CSP)
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Immunotherapies have transformed cancer care but face challenges such as low response rates, toxicities, and incomplete understanding of tumor immunobiology. A multiplex panel of proteomic assays targeting tumor-related proteins in tissue and plasma has been developed, showing impressive performance metrics and potential for future research use.
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.
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