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Development of a reliable and accurate algorithm to quantify the tumor immune stroma (QTiS) across tumor types

The tumor microenvironment plays an important role in the tumor biology. Overall survival of tumor patients after resection is influenced by tumor-infiltrating lymphocytes (TILs) as a component of the tumor stroma. However, it is not clear how to assess TILs in the tumor stroma due to heterogeneous...

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Autores principales: Miksch, Rainer Christoph, Hao, Jingcheng, Schoenberg, Markus Bo, Dötzer, Katharina, Schlüter, Friederike, Weniger, Maximilian, Yin, Shuai, Ormanns, Steffen, D'Haese, Jan Goesta, Guba, Markus Otto, Werner, Jens, Mayer, Barbara, Bazhin, Alexandr V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5777743/
https://www.ncbi.nlm.nih.gov/pubmed/29383131
http://dx.doi.org/10.18632/oncotarget.22932
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author Miksch, Rainer Christoph
Hao, Jingcheng
Schoenberg, Markus Bo
Dötzer, Katharina
Schlüter, Friederike
Weniger, Maximilian
Yin, Shuai
Ormanns, Steffen
D'Haese, Jan Goesta
Guba, Markus Otto
Werner, Jens
Mayer, Barbara
Bazhin, Alexandr V.
author_facet Miksch, Rainer Christoph
Hao, Jingcheng
Schoenberg, Markus Bo
Dötzer, Katharina
Schlüter, Friederike
Weniger, Maximilian
Yin, Shuai
Ormanns, Steffen
D'Haese, Jan Goesta
Guba, Markus Otto
Werner, Jens
Mayer, Barbara
Bazhin, Alexandr V.
author_sort Miksch, Rainer Christoph
collection PubMed
description The tumor microenvironment plays an important role in the tumor biology. Overall survival of tumor patients after resection is influenced by tumor-infiltrating lymphocytes (TILs) as a component of the tumor stroma. However, it is not clear how to assess TILs in the tumor stroma due to heterogeneous methods in different cancer types. Therefore, we present a novel Quantification of the Tumor immune Stroma (QTiS) Algorithm to reliably and accurately quantify cells in the tumor stroma. Immunohistochemical staining of CD3 and CD8 cells in sections of metastatic colorectal cancer (mCRC), ovarian cancer (OvCa), hepatocellular carcinoma (HCC), and pancreatic ductal adenocarcinoma (PDAC), alltogether N = 80, was performed. Hot spots of infiltrating immune cells are reported in the literature. Reliability of the hot spot identification of TILs was examined by two blinded observers. Accuracy was tested in 1 and 3 hot spots using computed counting methods (ZEN 2 software counting (ZC), ImageJ software with subjective threshold (ISC) and ImageJ with color deconvolution (IAC)) and compared to manual counting. All tumor types investigated showed an accumulation of TILs in the tumor stroma (peri- and intratumoral). Reliability between observers indicated a high level consistency. Accuracy for CD8+/CD3+ ratio and absolute cell count required 1 and 3 hot spots, respectively. ISC was found to be the best for paraffin sections, whereas IAC was ideal for frozen sections. ImageJ software is cost-effective and yielded the best results. In conclusion, an algorithm for quantification of tumoral stroma could be established. With this QTiS Algorithm counting of tumor stromal cells is reliable, accurate, and cost-effective.
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spelling pubmed-57777432018-01-30 Development of a reliable and accurate algorithm to quantify the tumor immune stroma (QTiS) across tumor types Miksch, Rainer Christoph Hao, Jingcheng Schoenberg, Markus Bo Dötzer, Katharina Schlüter, Friederike Weniger, Maximilian Yin, Shuai Ormanns, Steffen D'Haese, Jan Goesta Guba, Markus Otto Werner, Jens Mayer, Barbara Bazhin, Alexandr V. Oncotarget Research Paper The tumor microenvironment plays an important role in the tumor biology. Overall survival of tumor patients after resection is influenced by tumor-infiltrating lymphocytes (TILs) as a component of the tumor stroma. However, it is not clear how to assess TILs in the tumor stroma due to heterogeneous methods in different cancer types. Therefore, we present a novel Quantification of the Tumor immune Stroma (QTiS) Algorithm to reliably and accurately quantify cells in the tumor stroma. Immunohistochemical staining of CD3 and CD8 cells in sections of metastatic colorectal cancer (mCRC), ovarian cancer (OvCa), hepatocellular carcinoma (HCC), and pancreatic ductal adenocarcinoma (PDAC), alltogether N = 80, was performed. Hot spots of infiltrating immune cells are reported in the literature. Reliability of the hot spot identification of TILs was examined by two blinded observers. Accuracy was tested in 1 and 3 hot spots using computed counting methods (ZEN 2 software counting (ZC), ImageJ software with subjective threshold (ISC) and ImageJ with color deconvolution (IAC)) and compared to manual counting. All tumor types investigated showed an accumulation of TILs in the tumor stroma (peri- and intratumoral). Reliability between observers indicated a high level consistency. Accuracy for CD8+/CD3+ ratio and absolute cell count required 1 and 3 hot spots, respectively. ISC was found to be the best for paraffin sections, whereas IAC was ideal for frozen sections. ImageJ software is cost-effective and yielded the best results. In conclusion, an algorithm for quantification of tumoral stroma could be established. With this QTiS Algorithm counting of tumor stromal cells is reliable, accurate, and cost-effective. Impact Journals LLC 2017-12-04 /pmc/articles/PMC5777743/ /pubmed/29383131 http://dx.doi.org/10.18632/oncotarget.22932 Text en Copyright: © 2017 Miksch et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Research Paper
Miksch, Rainer Christoph
Hao, Jingcheng
Schoenberg, Markus Bo
Dötzer, Katharina
Schlüter, Friederike
Weniger, Maximilian
Yin, Shuai
Ormanns, Steffen
D'Haese, Jan Goesta
Guba, Markus Otto
Werner, Jens
Mayer, Barbara
Bazhin, Alexandr V.
Development of a reliable and accurate algorithm to quantify the tumor immune stroma (QTiS) across tumor types
title Development of a reliable and accurate algorithm to quantify the tumor immune stroma (QTiS) across tumor types
title_full Development of a reliable and accurate algorithm to quantify the tumor immune stroma (QTiS) across tumor types
title_fullStr Development of a reliable and accurate algorithm to quantify the tumor immune stroma (QTiS) across tumor types
title_full_unstemmed Development of a reliable and accurate algorithm to quantify the tumor immune stroma (QTiS) across tumor types
title_short Development of a reliable and accurate algorithm to quantify the tumor immune stroma (QTiS) across tumor types
title_sort development of a reliable and accurate algorithm to quantify the tumor immune stroma (qtis) across tumor types
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5777743/
https://www.ncbi.nlm.nih.gov/pubmed/29383131
http://dx.doi.org/10.18632/oncotarget.22932
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