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

被引：419

作者：

Tsujikawa, Takahiro ^{[1
,2
]}

Kumar, Sushil ^{[1
]}

Borkar, Rohan N. ^{[10
]}

Azimi, Vahid ^{[10
]}

Thibault, Guillaume ^{[3
]}

Chang, Young Hwan ^{[3
,4
]}

Balter, Ariel ^{[4
]}

Kawashima, Rie ^{[1
]}

Choe, Gina ^{[1
]}

Sauer, David ^{[5
]}

El Rassi, Edward ^{[2
]}

Clayburgh, Daniel R. ^{[2
,9
]}

Kulesz-Martin, Molly F. ^{[1
,6
,9
]}

Lutz, Eric R. ^{[11
,14
,15
]}

Zheng, Lei ^{[11
,12
,14
,15
]}

Jaffee, Elizabeth M. ^{[11
,13
,14
,15
]}

Leyshock, Patrick ^{[4
]}

Margolin, Adam A. ^{[4
,7
,9
]}

Mori, Motomi ^{[8
,9
]}

Gray, Joe W. ^{[3
,7
,9
]}

Flint, Paul W. ^{[2
,9
]}

Coussens, Lisa M. ^{[1
,9
]}

机构：

[1] Oregon Hlth & Sci Univ, Dept Cell Dev & Canc Biol, Portland, OR 97239 USA

[2] Oregon Hlth & Sci Univ, Dept Otolaryngol Head & Neck Surg, Portland, OR 97239 USA

[3] Oregon Hlth & Sci Univ, Dept Biomed Engn, Portland, OR 97239 USA

[4] Oregon Hlth & Sci Univ, Dept Computat Biol, Portland, OR 97239 USA

[5] Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97239 USA

[6] Oregon Hlth & Sci Univ, Dept Dermatol, Portland, OR 97239 USA

[7] Oregon Hlth & Sci Univ, OHSU Ctr Spatial Syst Biomed, Portland, OR 97239 USA

[8] Oregon Hlth & Sci Univ, Sch Publ Hlth, Portland, OR 97239 USA

[9] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97239 USA

[10] Intel Corp, Intel Hlth & Life Sci, Hillsboro, OR 97124 USA

[11] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA

[12] Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21205 USA

[13] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA

[14] Johns Hopkins Univ, Sch Med, Sidney Kimmel Canc Ctr, Baltimore, MD 21205 USA

[15] Johns Hopkins Univ, Sch Med, Skip Viragh Ctr Pancreat Canc Res & Clin Care, Baltimore, MD 21205 USA

来源：

CELL REPORTS | 2017年 / 19卷 / 01期

关键词：

CANCER-IMMUNOTHERAPY; PANCREATIC TUMORS; IMAGE-ANALYSIS; T-CELLS; EXPRESSION; CHEMOTHERAPY; MACROPHAGES; RESISTANCE; INTENSITY; BLOCKADE;

D O I：

10.1016/j.celrep.2017.03.037

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：203 / 217

页数：15

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