Journal
CELL REPORTS
Volume 19, Issue 1, Pages 203-217Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2017.03.037
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Funding
- Oregon Clinical and Translational Research Institute (OCTRI) [UL1TR000128]
- National Center for Advancing Translational Sciences (NCATS) at the NIH
- Stand Up To Cancer-Lustgarten Foundation Pancreatic Cancer Convergence Dream Team Translational Research Grant
- OHSU Knight Cancer Institute [P30 CA069533-17]
- NCI [CA192405]
- NIH/NCI
- DOD BCRP Era of Hope Scholar Expansion Award
- Breast Cancer Research Foundation
- Susan B. Komen Foundation
- Brenden-Colson Center for Pancreatic Health
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Here, we describe a multiplexed immunohistochemical platform with computational image processing workflows, including image cytometry, enabling simultaneous evaluation of 12 biomarkers in one formalin-fixed paraffin-embedded tissue section. To validate this platform, we used tissue microarrays containing 38 archival head and neck squamous cell carcinomas and revealed differential immune profiles based on lymphoid and myeloid cell densities, correlating with human papilloma virus status and prognosis. Based on these results, we investigated 24 pancreatic ductal adenocarcinomas from patients who received neoadjuvant GVAX vaccination and revealed that response to therapy correlated with degree of mono-myelocytic cell density and percentages of CD8(+) T cells expressing T cell exhaustion markers. These data highlight the utility of in situ immune monitoring for patient stratification and provide digital image processing pipelines to the community for examining immune complexity in precious tissue sections, where phenotype and tissue architecture are preserved to improve biomarker discovery and assessment.
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