@article{94105c41da6340fe954406d088ba205a,
title = "Quantitative Multiplex Immunohistochemistry Reveals Myeloid-Inflamed Tumor-Immune Complexity Associated with Poor Prognosis",
abstract = "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.",
keywords = "cancer immunology, digital pathology, head and neck cancer, image cytometry, immunohistochemistry, multiplex, pancreatic cancer, tissue biomarker",
author = "Takahiro Tsujikawa and Sushil Kumar and Borkar, {Rohan N.} and Vahid Azimi and Guillaume Thibault and Chang, {Young Hwan} and Ariel Balter and Rie Kawashima and Gina Choe and David Sauer and {El Rassi}, Edward and Clayburgh, {Daniel R.} and Kulesz-Martin, {Molly F.} and Lutz, {Eric R.} and Lei Zheng and Jaffee, {Elizabeth M.} and Patrick Leyshock and Adam Margolin and Mori, {Motomi (Tomi)} and Gray, {Joe W.} and Flint, {Paul W.} and Coussens, {Lisa M.}",
note = "Funding Information: The authors thank Justin Tibbitts, Teresa Beechwood, and Chase Smith for regulatory and technical assistance and Dr. Gunderson for FACS analysis. This project was supported by the Oregon Clinical and Translational Research Institute (OCTRI, UL1TR000128), the National Center for Advancing Translational Sciences (NCATS) at the NIH, a Stand Up To Cancer-Lustgarten Foundation Pancreatic Cancer Convergence Dream Team Translational Research Grant (L.M.C., A.A.M., and E.M.J.), and the OHSU Knight Cancer Institute (P30 CA069533-17). M.F.K.-M. acknowledges support from the NCI (CA192405). L.M.C. acknowledges support from the NIH/NCI, DOD BCRP Era of Hope Scholar Expansion Award, Breast Cancer Research Foundation, Susan B. Komen Foundation, and Brenden-Colson Center for Pancreatic Health. A patent application related to the methodology described in the present work has been filed by T.T., S.K., R.N.B., V.A., and L.M.C. Publisher Copyright: {\textcopyright} 2017 The Author(s)",
year = "2017",
month = apr,
day = "4",
doi = "10.1016/j.celrep.2017.03.037",
language = "English (US)",
volume = "19",
pages = "203--217",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "1",
}