Gastric Carcinomas with Stromal B7-H3 Expression Have Lower Intratumoural CD8+ T Cell Density

CD8+ T cells are the main effector cells of anti-cancer immune response that can be regulated by various costimulatory and coinhibitory molecules, including members of the B7 family. B7 homolog 3 (B7-H3) appears as a promising marker for immunotherapy; however, its significance in gastric cancer (GC...

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Main Authors: Dita Ulase, Hans-Michael Behrens, Sandra Krüger, Sebastian Zeissig, Christoph Röcken
Format: Article
Language:English
Published: MDPI AG 2021-02-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/22/4/2129
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author Dita Ulase
Hans-Michael Behrens
Sandra Krüger
Sebastian Zeissig
Christoph Röcken
author_facet Dita Ulase
Hans-Michael Behrens
Sandra Krüger
Sebastian Zeissig
Christoph Röcken
author_sort Dita Ulase
collection DOAJ
description CD8+ T cells are the main effector cells of anti-cancer immune response that can be regulated by various costimulatory and coinhibitory molecules, including members of the B7 family. B7 homolog 3 (B7-H3) appears as a promising marker for immunotherapy; however, its significance in gastric cancer (GC) is unclear yet. We evaluated the spatial distribution of CD8+ T cells in relation to the expression of B7-H3 by double immunohistochemical staining. The level of B7-H3 intensity was scored manually (0–3) and dichotomized into B7-H3-low and B7-H3-high groups. The distribution and density of CD8+ T cells was analysed using whole slide digital imaging. B7-H3 was expressed mainly in the stromal compartment of GC (<i>n</i> = 73, 76% of all cases). Tumours with high expression of B7-H3 showed larger spatial differences of CD8+ T cells (86.4/mm<sup>2</sup> in tumour centre vs. 414.9/mm<sup>2</sup> in invasive front) when compared to B7-H3-low group (157.7/mm<sup>2</sup> vs. 218.7/mm<sup>2</sup>, respectively) (<i>p</i> < 0.001). This study provides insight into the expression pattern of B7-H3 in GC of Western origin. In GCs with higher level of B7-H3 expression, CD8+ T cells were spatially suppressed in the tumour centre suggesting that B7-H3 might be involved in tumour escape mechanisms from the immune response.
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spelling doaj.art-e8218d603926476eb6ba0f8797e8d2082023-12-11T17:51:31ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-02-01224212910.3390/ijms22042129Gastric Carcinomas with Stromal B7-H3 Expression Have Lower Intratumoural CD8+ T Cell DensityDita Ulase0Hans-Michael Behrens1Sandra Krüger2Sebastian Zeissig3Christoph Röcken4Department of Pathology, Christian-Albrechts-University, 24105 Kiel, GermanyDepartment of Pathology, Christian-Albrechts-University, 24105 Kiel, GermanyDepartment of Pathology, Christian-Albrechts-University, 24105 Kiel, GermanyDepartment of Medicine I, University Medical Center Dresden, Technische Universität (TU) Dresden, 01307 Dresden, GermanyDepartment of Pathology, Christian-Albrechts-University, 24105 Kiel, GermanyCD8+ T cells are the main effector cells of anti-cancer immune response that can be regulated by various costimulatory and coinhibitory molecules, including members of the B7 family. B7 homolog 3 (B7-H3) appears as a promising marker for immunotherapy; however, its significance in gastric cancer (GC) is unclear yet. We evaluated the spatial distribution of CD8+ T cells in relation to the expression of B7-H3 by double immunohistochemical staining. The level of B7-H3 intensity was scored manually (0–3) and dichotomized into B7-H3-low and B7-H3-high groups. The distribution and density of CD8+ T cells was analysed using whole slide digital imaging. B7-H3 was expressed mainly in the stromal compartment of GC (<i>n</i> = 73, 76% of all cases). Tumours with high expression of B7-H3 showed larger spatial differences of CD8+ T cells (86.4/mm<sup>2</sup> in tumour centre vs. 414.9/mm<sup>2</sup> in invasive front) when compared to B7-H3-low group (157.7/mm<sup>2</sup> vs. 218.7/mm<sup>2</sup>, respectively) (<i>p</i> < 0.001). This study provides insight into the expression pattern of B7-H3 in GC of Western origin. In GCs with higher level of B7-H3 expression, CD8+ T cells were spatially suppressed in the tumour centre suggesting that B7-H3 might be involved in tumour escape mechanisms from the immune response.https://www.mdpi.com/1422-0067/22/4/2129B7-H3CD8-Positive T-Lymphocytesgastric cancerimmune checkpointimmune evasionimmunohistochemistry
spellingShingle Dita Ulase
Hans-Michael Behrens
Sandra Krüger
Sebastian Zeissig
Christoph Röcken
Gastric Carcinomas with Stromal B7-H3 Expression Have Lower Intratumoural CD8+ T Cell Density
International Journal of Molecular Sciences
B7-H3
CD8-Positive T-Lymphocytes
gastric cancer
immune checkpoint
immune evasion
immunohistochemistry
title Gastric Carcinomas with Stromal B7-H3 Expression Have Lower Intratumoural CD8+ T Cell Density
title_full Gastric Carcinomas with Stromal B7-H3 Expression Have Lower Intratumoural CD8+ T Cell Density
title_fullStr Gastric Carcinomas with Stromal B7-H3 Expression Have Lower Intratumoural CD8+ T Cell Density
title_full_unstemmed Gastric Carcinomas with Stromal B7-H3 Expression Have Lower Intratumoural CD8+ T Cell Density
title_short Gastric Carcinomas with Stromal B7-H3 Expression Have Lower Intratumoural CD8+ T Cell Density
title_sort gastric carcinomas with stromal b7 h3 expression have lower intratumoural cd8 t cell density
topic B7-H3
CD8-Positive T-Lymphocytes
gastric cancer
immune checkpoint
immune evasion
immunohistochemistry
url https://www.mdpi.com/1422-0067/22/4/2129
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AT sebastianzeissig gastriccarcinomaswithstromalb7h3expressionhavelowerintratumouralcd8tcelldensity
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