CD8+ and Regulatory T cells Differentiate Tumor Immune Phenotypes and Predict Survival in Locally Advanced Head and Neck Cancer

Background: The tumor immune status “inflamed”, “immune excluded”, and “desert” might serve as a predictive parameter. We studied these three cancer immune phenotypes while using a simple immunohistochemical algorithm. Methods: Pre-treatmen...

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Main Authors: Alessia Echarti, Markus Hecht, Maike Büttner-Herold, Marlen Haderlein, Arndt Hartmann, Rainer Fietkau, Luitpold Distel
Format: Article
Language:English
Published: MDPI AG 2019-09-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/11/9/1398
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spelling doaj-70db7dfaeeb447e389feba250c1368402020-11-24T20:53:57ZengMDPI AGCancers2072-66942019-09-01119139810.3390/cancers11091398cancers11091398CD8+ and Regulatory T cells Differentiate Tumor Immune Phenotypes and Predict Survival in Locally Advanced Head and Neck CancerAlessia Echarti0Markus Hecht1Maike Büttner-Herold2Marlen Haderlein3Arndt Hartmann4Rainer Fietkau5Luitpold Distel6Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, D-91054 Erlangen, GermanyDepartment of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, D-91054 Erlangen, GermanyDepartment of Nephropathology, Institute of Pathology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, D-91054 Erlangen, GermanyDepartment of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, D-91054 Erlangen, GermanyInstitute of Pathology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, GermanyDepartment of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, D-91054 Erlangen, GermanyDepartment of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, D-91054 Erlangen, GermanyBackground: The tumor immune status &#8220;inflamed&#8221;, &#8220;immune excluded&#8221;, and &#8220;desert&#8221; might serve as a predictive parameter. We studied these three cancer immune phenotypes while using a simple immunohistochemical algorithm. Methods: Pre-treatment tissue samples of 280 patients with locally advanced HNSCC treated with radiochemotherapy were analyzed. A double staining of CD8+ cytotoxic T cells (CTL) and FoxP3+ (Treg) was performed and the cell density was evaluated in the intraepithelial and stromal compartment of the tumor. Results: The classification of tumors as &#8220;immune desert&#8221; when stromal CTL were &#8804; 50 cells/mm<sup>2</sup>, &#8220;inflamed&#8221; when intraepithelial CTL were &gt; 500 cells/mm<sup>2</sup>, and as &#8220;excluded&#8221; when neither of these definitions met these cut off values allowed the best discrimination regarding overall survival. These groups had median OS periods of 37, 61, and 85 months, respectively. In &#8220;immune desert&#8221; and &#8220;immune excluded&#8221; tumors high Treg tended to worsen OS, but in &#8220;inflamed&#8221; tumors high Treg clearly improved OS. Conclusions: We propose that, in locally advanced HNSCC, the tumor immune state &#8220;inflamed&#8221;, &#8220;immune excluded&#8221;, and &#8220;immune desert&#8221; can be defined by intraepithelial and stromal CTL. Tregs can further subdivide these groups. The opposing effects of Tregs in the different groups might be the reason for the inconsistency of Tregs prognostic values published earlier.https://www.mdpi.com/2072-6694/11/9/1398CD8+regulatory T cellsFoxP3+head and neck squamous cell carcinomaimmune dessertinflamedexcluded
collection DOAJ
language English
format Article
sources DOAJ
author Alessia Echarti
Markus Hecht
Maike Büttner-Herold
Marlen Haderlein
Arndt Hartmann
Rainer Fietkau
Luitpold Distel
spellingShingle Alessia Echarti
Markus Hecht
Maike Büttner-Herold
Marlen Haderlein
Arndt Hartmann
Rainer Fietkau
Luitpold Distel
CD8+ and Regulatory T cells Differentiate Tumor Immune Phenotypes and Predict Survival in Locally Advanced Head and Neck Cancer
Cancers
CD8+
regulatory T cells
FoxP3+
head and neck squamous cell carcinoma
immune dessert
inflamed
excluded
author_facet Alessia Echarti
Markus Hecht
Maike Büttner-Herold
Marlen Haderlein
Arndt Hartmann
Rainer Fietkau
Luitpold Distel
author_sort Alessia Echarti
title CD8+ and Regulatory T cells Differentiate Tumor Immune Phenotypes and Predict Survival in Locally Advanced Head and Neck Cancer
title_short CD8+ and Regulatory T cells Differentiate Tumor Immune Phenotypes and Predict Survival in Locally Advanced Head and Neck Cancer
title_full CD8+ and Regulatory T cells Differentiate Tumor Immune Phenotypes and Predict Survival in Locally Advanced Head and Neck Cancer
title_fullStr CD8+ and Regulatory T cells Differentiate Tumor Immune Phenotypes and Predict Survival in Locally Advanced Head and Neck Cancer
title_full_unstemmed CD8+ and Regulatory T cells Differentiate Tumor Immune Phenotypes and Predict Survival in Locally Advanced Head and Neck Cancer
title_sort cd8+ and regulatory t cells differentiate tumor immune phenotypes and predict survival in locally advanced head and neck cancer
publisher MDPI AG
series Cancers
issn 2072-6694
publishDate 2019-09-01
description Background: The tumor immune status &#8220;inflamed&#8221;, &#8220;immune excluded&#8221;, and &#8220;desert&#8221; might serve as a predictive parameter. We studied these three cancer immune phenotypes while using a simple immunohistochemical algorithm. Methods: Pre-treatment tissue samples of 280 patients with locally advanced HNSCC treated with radiochemotherapy were analyzed. A double staining of CD8+ cytotoxic T cells (CTL) and FoxP3+ (Treg) was performed and the cell density was evaluated in the intraepithelial and stromal compartment of the tumor. Results: The classification of tumors as &#8220;immune desert&#8221; when stromal CTL were &#8804; 50 cells/mm<sup>2</sup>, &#8220;inflamed&#8221; when intraepithelial CTL were &gt; 500 cells/mm<sup>2</sup>, and as &#8220;excluded&#8221; when neither of these definitions met these cut off values allowed the best discrimination regarding overall survival. These groups had median OS periods of 37, 61, and 85 months, respectively. In &#8220;immune desert&#8221; and &#8220;immune excluded&#8221; tumors high Treg tended to worsen OS, but in &#8220;inflamed&#8221; tumors high Treg clearly improved OS. Conclusions: We propose that, in locally advanced HNSCC, the tumor immune state &#8220;inflamed&#8221;, &#8220;immune excluded&#8221;, and &#8220;immune desert&#8221; can be defined by intraepithelial and stromal CTL. Tregs can further subdivide these groups. The opposing effects of Tregs in the different groups might be the reason for the inconsistency of Tregs prognostic values published earlier.
topic CD8+
regulatory T cells
FoxP3+
head and neck squamous cell carcinoma
immune dessert
inflamed
excluded
url https://www.mdpi.com/2072-6694/11/9/1398
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