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 & 2 others Paul W. Flint, Lisa M. Coussens

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)203-217
Number of pages15
JournalCell Reports
Volume19
Issue number1
DOIs
StatePublished - Apr 4 2017

Fingerprint

Immunohistochemistry
Neoplasms
Library Catalogs
Cell Count
Biological Markers
T-Lymphocytes
T-cells
Biomarkers
Image processing
Image Cytometry
Immunologic Monitoring
Workflow
Papilloma
Myeloid Cells
Paraffin
Formaldehyde
Squamous Cell Carcinoma
Vaccination
Adenocarcinoma
Neck

Keywords

  • cancer immunology
  • digital pathology
  • head and neck cancer
  • image cytometry
  • immunohistochemistry
  • multiplex
  • pancreatic cancer
  • tissue biomarker

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Tsujikawa, T., Kumar, S., Borkar, R. N., Azimi, V., Thibault, G., Chang, Y. H., ... Coussens, L. M. (2017). Quantitative Multiplex Immunohistochemistry Reveals Myeloid-Inflamed Tumor-Immune Complexity Associated with Poor Prognosis. Cell Reports, 19(1), 203-217. DOI: 10.1016/j.celrep.2017.03.037

Quantitative Multiplex Immunohistochemistry Reveals Myeloid-Inflamed Tumor-Immune Complexity Associated with Poor Prognosis. / Tsujikawa, Takahiro; Kumar, Sushil; Borkar, Rohan N.; Azimi, Vahid; Thibault, Guillaume; Chang, Young Hwan; Balter, Ariel; Kawashima, Rie; Choe, Gina; Sauer, David; El Rassi, Edward; Clayburgh, Daniel R.; Kulesz-Martin, Molly F.; Lutz, Eric R.; Zheng, Lei; Jaffee, Elizabeth M.; Leyshock, Patrick; Margolin, Adam A.; Mori, Motomi; Gray, Joe W.; Flint, Paul W.; Coussens, Lisa M.

In: Cell Reports, Vol. 19, No. 1, 04.04.2017, p. 203-217.

Research output: Contribution to journalArticle

Tsujikawa, T, Kumar, S, Borkar, RN, Azimi, V, Thibault, G, Chang, YH, Balter, A, Kawashima, R, Choe, G, Sauer, D, El Rassi, E, Clayburgh, DR, Kulesz-Martin, MF, Lutz, ER, Zheng, L, Jaffee, EM, Leyshock, P, Margolin, AA, Mori, M, Gray, JW, Flint, PW & Coussens, LM 2017, 'Quantitative Multiplex Immunohistochemistry Reveals Myeloid-Inflamed Tumor-Immune Complexity Associated with Poor Prognosis' Cell Reports, vol 19, no. 1, pp. 203-217. DOI: 10.1016/j.celrep.2017.03.037
Tsujikawa T, Kumar S, Borkar RN, Azimi V, Thibault G, Chang YH et al. Quantitative Multiplex Immunohistochemistry Reveals Myeloid-Inflamed Tumor-Immune Complexity Associated with Poor Prognosis. Cell Reports. 2017 Apr 4;19(1):203-217. Available from, DOI: 10.1016/j.celrep.2017.03.037

Tsujikawa, Takahiro; Kumar, Sushil; Borkar, Rohan N.; Azimi, Vahid; Thibault, Guillaume; Chang, Young Hwan; Balter, Ariel; Kawashima, Rie; Choe, Gina; Sauer, David; El Rassi, Edward; Clayburgh, Daniel R.; Kulesz-Martin, Molly F.; Lutz, Eric R.; Zheng, Lei; Jaffee, Elizabeth M.; Leyshock, Patrick; Margolin, Adam A.; Mori, Motomi; Gray, Joe W.; Flint, Paul W.; Coussens, Lisa M. / Quantitative Multiplex Immunohistochemistry Reveals Myeloid-Inflamed Tumor-Immune Complexity Associated with Poor Prognosis.

In: Cell Reports, Vol. 19, No. 1, 04.04.2017, p. 203-217.

Research output: Contribution to journalArticle

@article{5f10178ecfdf4893bd4fdfa88739284b,
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 Margolin, {Adam A.} and Motomi Mori and Gray, {Joe W.} and Flint, {Paul W.} and Coussens, {Lisa M.}",
year = "2017",
month = "4",
doi = "10.1016/j.celrep.2017.03.037",
volume = "19",
pages = "203--217",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "1",

}

TY - JOUR

T1 - Quantitative Multiplex Immunohistochemistry Reveals Myeloid-Inflamed Tumor-Immune Complexity Associated with Poor Prognosis

AU - Tsujikawa,Takahiro

AU - Kumar,Sushil

AU - Borkar,Rohan N.

AU - Azimi,Vahid

AU - Thibault,Guillaume

AU - Chang,Young Hwan

AU - Balter,Ariel

AU - Kawashima,Rie

AU - Choe,Gina

AU - Sauer,David

AU - El Rassi,Edward

AU - Clayburgh,Daniel R.

AU - Kulesz-Martin,Molly F.

AU - Lutz,Eric R.

AU - Zheng,Lei

AU - Jaffee,Elizabeth M.

AU - Leyshock,Patrick

AU - Margolin,Adam A.

AU - Mori,Motomi

AU - Gray,Joe W.

AU - Flint,Paul W.

AU - Coussens,Lisa M.

PY - 2017/4/4

Y1 - 2017/4/4

N2 - 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.

AB - 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.

KW - cancer immunology

KW - digital pathology

KW - head and neck cancer

KW - image cytometry

KW - immunohistochemistry

KW - multiplex

KW - pancreatic cancer

KW - tissue biomarker

UR - http://www.scopus.com/inward/record.url?scp=85016985952&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85016985952&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2017.03.037

DO - 10.1016/j.celrep.2017.03.037

M3 - Article

VL - 19

SP - 203

EP - 217

JO - Cell Reports

T2 - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 1

ER -