Quantitative Multiplex Immunohistochemistry Reveals Myeloid-Inflamed Tumor-Immune Complexity Associated with Poor Prognosis

Takahiro Tsujikawa; Sushil Kumar; Rohan N. Borkar; Vahid Azimi; Guillaume Thibault; Young Hwan Chang; Ariel Balter; Rie Kawashima; Gina Choe; David Sauer; Edward El Rassi; Daniel R. Clayburgh; Molly F. Kulesz-Martin; Eric R. Lutz; Lei Zheng; Elizabeth M. Jaffee; Patrick Leyshock; Adam A. Margolin; Motomi Mori; Joe W. Gray; Paul W. Flint; Lisa M. Coussens

doi:10.1016/j.celrep.2017.03.037

Cell Reports (Apr 2017)

Quantitative Multiplex Immunohistochemistry Reveals Myeloid-Inflamed Tumor-Immune Complexity Associated with Poor Prognosis

Takahiro Tsujikawa,
Sushil Kumar,
Rohan N. Borkar,
Vahid Azimi,
Guillaume Thibault,
Young Hwan Chang,
Ariel Balter,
Rie Kawashima,
Gina Choe,
David Sauer,
Edward El Rassi,
Daniel R. Clayburgh,
Molly F. Kulesz-Martin,
Eric R. Lutz,
Lei Zheng,
Elizabeth M. Jaffee,
Patrick Leyshock,
Adam A. Margolin,
Motomi Mori,
Joe W. Gray,
Paul W. Flint,
Lisa M. Coussens

Affiliations

Takahiro Tsujikawa: Department of Cell, Developmental & Cancer Biology, Oregon Health and Science University, Portland, OR 97239, USA
Sushil Kumar: Department of Cell, Developmental & Cancer Biology, Oregon Health and Science University, Portland, OR 97239, USA
Rohan N. Borkar: Intel Health and Life Sciences, Intel Corporation, Hillsboro, OR 97124, USA
Vahid Azimi: Intel Health and Life Sciences, Intel Corporation, Hillsboro, OR 97124, USA
Guillaume Thibault: Department of Biomedical Engineering, Oregon Health and Science University, Portland, OR 97239, USA
Young Hwan Chang: Department of Biomedical Engineering, Oregon Health and Science University, Portland, OR 97239, USA
Ariel Balter: Department of Computational Biology, Oregon Health and Science University, Portland, OR 97239, USA
Rie Kawashima: Department of Cell, Developmental & Cancer Biology, Oregon Health and Science University, Portland, OR 97239, USA
Gina Choe: Department of Cell, Developmental & Cancer Biology, Oregon Health and Science University, Portland, OR 97239, USA
David Sauer: Department of Pathology, Oregon Health and Science University, Portland, OR 97239, USA
Edward El Rassi: Department of Otolaryngology-Head and Neck Surgery, Oregon Health and Science University, Portland, OR 97239, USA
Daniel R. Clayburgh: Department of Otolaryngology-Head and Neck Surgery, Oregon Health and Science University, Portland, OR 97239, USA
Molly F. Kulesz-Martin: Department of Cell, Developmental & Cancer Biology, Oregon Health and Science University, Portland, OR 97239, USA
Eric R. Lutz: Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Lei Zheng: Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Elizabeth M. Jaffee: Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Patrick Leyshock: Department of Computational Biology, Oregon Health and Science University, Portland, OR 97239, USA
Adam A. Margolin: Department of Computational Biology, Oregon Health and Science University, Portland, OR 97239, USA
Motomi Mori: School of Public Health, Oregon Health and Science University, Portland, OR 97239, USA
Joe W. Gray: Department of Biomedical Engineering, Oregon Health and Science University, Portland, OR 97239, USA
Paul W. Flint: Department of Otolaryngology-Head and Neck Surgery, Oregon Health and Science University, Portland, OR 97239, USA
Lisa M. Coussens: Department of Cell, Developmental & Cancer Biology, Oregon Health and Science University, Portland, OR 97239, USA

DOI: https://doi.org/10.1016/j.celrep.2017.03.037
Journal volume & issue: Vol. 19, no. 1
pp. 203 – 217

Abstract

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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.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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