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: Research - peer-reviewArticle

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.

LanguageEnglish (US)
Pages203-217
Number of pages15
JournalCell Reports
Volume19
Issue number1
DOIs
StatePublished - Apr 4 2017

Fingerprint

Immunohistochemistry
Neoplasms
Tumors
Tissue
Cell Count
Biomarkers
T-Lymphocytes
T-cells
Image processing
Papillomaviridae
Image Cytometry
Immunologic Monitoring
Workflow
Myeloid Cells
Paraffin
Formaldehyde
Vaccination
Adenocarcinoma
Lymphocytes
Phenotype

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: Research - peer-reviewArticle

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. 2017 ; Vol. 19, No. 1. pp. 203-217
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