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The Major Role of NF-κB in the Depth of Invasion on Acral Melanoma by Decreasing CD8(+) T Cells

BACKGROUND: The tumor microenvironment including immune surveillance affects malignant melanoma (MM) behavior. Nuclear factor κB (NF-κB) stimulates the transcription of various genes in the nucleus and plays a role in the inflammatory process and in tumorigenesis. CD8(+) T cells have cytotoxic prope...

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Autores principales: Usman, Hermin Aminah, Hernowo, Bethy S., Tobing, Maringan Diapari Lumban, Hindritiani, Reti
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Korean Society of Pathologists and the Korean Society for Cytopathology 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5964292/
https://www.ncbi.nlm.nih.gov/pubmed/29673240
http://dx.doi.org/10.4132/jptm.2018.04.04
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author Usman, Hermin Aminah
Hernowo, Bethy S.
Tobing, Maringan Diapari Lumban
Hindritiani, Reti
author_facet Usman, Hermin Aminah
Hernowo, Bethy S.
Tobing, Maringan Diapari Lumban
Hindritiani, Reti
author_sort Usman, Hermin Aminah
collection PubMed
description BACKGROUND: The tumor microenvironment including immune surveillance affects malignant melanoma (MM) behavior. Nuclear factor κB (NF-κB) stimulates the transcription of various genes in the nucleus and plays a role in the inflammatory process and in tumorigenesis. CD8(+) T cells have cytotoxic properties important in the elimination of tumors. However, inhibitory receptors on the cell surface will bind to programmed death-ligand 1 (PD-L1), causing CD8(+) T cells to lose their ability to initiate an immune response. This study analyzed the association of NF-κB and PD-L1 expression levels and CD8(+) T-cell counts with depth of invasion of acral MM, which may be a predictor of aggressiveness related to an increased risk of metastasis. METHODS: A retrospective cross-sectional study was conducted in the Department of Anatomical Pathology, Faculty of Medicine, Universitas Padjadjaran/Hasan Sadikin Hospital using 96 cases of acral melanoma. Immunohistochemical staining was performed on paraffin blocks using anti–NF-κB, –PD-L1, and -CD8 antibodies and invasion depth was measured using dotSlide-imaging software. RESULTS: The study showed significant associations between the individual expression of NF-κB and PD-L1 and CD8(+) T-cell number, with MM invasion depth. NF-κB was found to be a confounding variable of CD8(+) T-cell number (p < .05), but not for PD-L1 expression (p = .154). Through multivariate analysis it was found that NF-κB had the greatest association with the depth of invasion (p < .001), whereas PD-L1 was unrelated to the depth of invasion because it depends on the number of CD8(+) T cells (p = .870). CONCLUSIONS: NF-κB plays a major role in acral MM invasion, by decreasing the number of CD8(+) T cells in acral MM.
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spelling pubmed-59642922018-05-31 The Major Role of NF-κB in the Depth of Invasion on Acral Melanoma by Decreasing CD8(+) T Cells Usman, Hermin Aminah Hernowo, Bethy S. Tobing, Maringan Diapari Lumban Hindritiani, Reti J Pathol Transl Med Original Article BACKGROUND: The tumor microenvironment including immune surveillance affects malignant melanoma (MM) behavior. Nuclear factor κB (NF-κB) stimulates the transcription of various genes in the nucleus and plays a role in the inflammatory process and in tumorigenesis. CD8(+) T cells have cytotoxic properties important in the elimination of tumors. However, inhibitory receptors on the cell surface will bind to programmed death-ligand 1 (PD-L1), causing CD8(+) T cells to lose their ability to initiate an immune response. This study analyzed the association of NF-κB and PD-L1 expression levels and CD8(+) T-cell counts with depth of invasion of acral MM, which may be a predictor of aggressiveness related to an increased risk of metastasis. METHODS: A retrospective cross-sectional study was conducted in the Department of Anatomical Pathology, Faculty of Medicine, Universitas Padjadjaran/Hasan Sadikin Hospital using 96 cases of acral melanoma. Immunohistochemical staining was performed on paraffin blocks using anti–NF-κB, –PD-L1, and -CD8 antibodies and invasion depth was measured using dotSlide-imaging software. RESULTS: The study showed significant associations between the individual expression of NF-κB and PD-L1 and CD8(+) T-cell number, with MM invasion depth. NF-κB was found to be a confounding variable of CD8(+) T-cell number (p < .05), but not for PD-L1 expression (p = .154). Through multivariate analysis it was found that NF-κB had the greatest association with the depth of invasion (p < .001), whereas PD-L1 was unrelated to the depth of invasion because it depends on the number of CD8(+) T cells (p = .870). CONCLUSIONS: NF-κB plays a major role in acral MM invasion, by decreasing the number of CD8(+) T cells in acral MM. The Korean Society of Pathologists and the Korean Society for Cytopathology 2018-05 2018-04-20 /pmc/articles/PMC5964292/ /pubmed/29673240 http://dx.doi.org/10.4132/jptm.2018.04.04 Text en © 2018 The Korean Society of Pathologists/The Korean Society for Cytopathology This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Usman, Hermin Aminah
Hernowo, Bethy S.
Tobing, Maringan Diapari Lumban
Hindritiani, Reti
The Major Role of NF-κB in the Depth of Invasion on Acral Melanoma by Decreasing CD8(+) T Cells
title The Major Role of NF-κB in the Depth of Invasion on Acral Melanoma by Decreasing CD8(+) T Cells
title_full The Major Role of NF-κB in the Depth of Invasion on Acral Melanoma by Decreasing CD8(+) T Cells
title_fullStr The Major Role of NF-κB in the Depth of Invasion on Acral Melanoma by Decreasing CD8(+) T Cells
title_full_unstemmed The Major Role of NF-κB in the Depth of Invasion on Acral Melanoma by Decreasing CD8(+) T Cells
title_short The Major Role of NF-κB in the Depth of Invasion on Acral Melanoma by Decreasing CD8(+) T Cells
title_sort major role of nf-κb in the depth of invasion on acral melanoma by decreasing cd8(+) t cells
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5964292/
https://www.ncbi.nlm.nih.gov/pubmed/29673240
http://dx.doi.org/10.4132/jptm.2018.04.04
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