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Transcriptional analysis highlights three distinct immune profiles of high-risk oral epithelial dysplasia

Oral potentially malignant disorders (OPMD) are precursors of oral squamous cell carcinoma (OSCC), and the presence of oral epithelial dysplasia (OED) in OPMD confers an increased risk of malignant transformation. Emerging evidence has indicated a role for the immune system in OPMD disease progressi...

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Autores principales: Gan, Chai Phei, Lee, Bernard Kok Bang, Lau, Shin Hin, Kallarakkal, Thomas George, Zaini, Zuraiza Mohamad, Lye, Bryan Kit Weng, Zain, Rosnah Binti, Sathasivam, Hans Prakash, Yeong, Joe Poh Sheng, Savelyeva, Natalia, Thomas, Gareth, Ottensmeier, Christian H., Ariffin, Hany, Cheong, Sok Ching, Lim, Kue Peng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9479061/
https://www.ncbi.nlm.nih.gov/pubmed/36119104
http://dx.doi.org/10.3389/fimmu.2022.954567
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author Gan, Chai Phei
Lee, Bernard Kok Bang
Lau, Shin Hin
Kallarakkal, Thomas George
Zaini, Zuraiza Mohamad
Lye, Bryan Kit Weng
Zain, Rosnah Binti
Sathasivam, Hans Prakash
Yeong, Joe Poh Sheng
Savelyeva, Natalia
Thomas, Gareth
Ottensmeier, Christian H.
Ariffin, Hany
Cheong, Sok Ching
Lim, Kue Peng
author_facet Gan, Chai Phei
Lee, Bernard Kok Bang
Lau, Shin Hin
Kallarakkal, Thomas George
Zaini, Zuraiza Mohamad
Lye, Bryan Kit Weng
Zain, Rosnah Binti
Sathasivam, Hans Prakash
Yeong, Joe Poh Sheng
Savelyeva, Natalia
Thomas, Gareth
Ottensmeier, Christian H.
Ariffin, Hany
Cheong, Sok Ching
Lim, Kue Peng
author_sort Gan, Chai Phei
collection PubMed
description Oral potentially malignant disorders (OPMD) are precursors of oral squamous cell carcinoma (OSCC), and the presence of oral epithelial dysplasia (OED) in OPMD confers an increased risk of malignant transformation. Emerging evidence has indicated a role for the immune system in OPMD disease progression; however, the underlying immune mechanisms remain elusive. In this study, we used immune signatures established from cancer to delineate the immune profiles of moderate and severe OED, which are considered high-risk OPMD. We demonstrated that moderate and severe OEDs exhibit high lymphocyte infiltration and upregulation of genes involved in both immune surveillance (major histocompatibility complex-I, T cells, B cells and cytolytic activity) and immune suppression (immune checkpoints, T regulatory cells, and tumor-associated macrophages). Notably, we identified three distinct subtypes of moderate and severe OED: immune cytotoxic, non-cytotoxic and non-immune reactive. Active immune surveillance is present in the immune cytotoxic subtype, whereas the non-cytotoxic subtype lacks CD8 immune cytotoxic response. The non-immune reactive subtype showed upregulation of genes involved in the stromal microenvironment and cell cycle. The lack of T cell infiltration and activation in the non-immune reactive subtype is due to the dysregulation of CTNNB1, PTEN and JAK2. This work suggests that moderate and severe OED that harbor the non-cytotoxic or non-immune reactive subtype are likely to progress to cancer. Overall, we showed that distinct immune responses are present in high-risk OPMD, and revealed targetable pathways that could lead to potential new approaches for non-surgical management of OED.
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spelling pubmed-94790612022-09-17 Transcriptional analysis highlights three distinct immune profiles of high-risk oral epithelial dysplasia Gan, Chai Phei Lee, Bernard Kok Bang Lau, Shin Hin Kallarakkal, Thomas George Zaini, Zuraiza Mohamad Lye, Bryan Kit Weng Zain, Rosnah Binti Sathasivam, Hans Prakash Yeong, Joe Poh Sheng Savelyeva, Natalia Thomas, Gareth Ottensmeier, Christian H. Ariffin, Hany Cheong, Sok Ching Lim, Kue Peng Front Immunol Immunology Oral potentially malignant disorders (OPMD) are precursors of oral squamous cell carcinoma (OSCC), and the presence of oral epithelial dysplasia (OED) in OPMD confers an increased risk of malignant transformation. Emerging evidence has indicated a role for the immune system in OPMD disease progression; however, the underlying immune mechanisms remain elusive. In this study, we used immune signatures established from cancer to delineate the immune profiles of moderate and severe OED, which are considered high-risk OPMD. We demonstrated that moderate and severe OEDs exhibit high lymphocyte infiltration and upregulation of genes involved in both immune surveillance (major histocompatibility complex-I, T cells, B cells and cytolytic activity) and immune suppression (immune checkpoints, T regulatory cells, and tumor-associated macrophages). Notably, we identified three distinct subtypes of moderate and severe OED: immune cytotoxic, non-cytotoxic and non-immune reactive. Active immune surveillance is present in the immune cytotoxic subtype, whereas the non-cytotoxic subtype lacks CD8 immune cytotoxic response. The non-immune reactive subtype showed upregulation of genes involved in the stromal microenvironment and cell cycle. The lack of T cell infiltration and activation in the non-immune reactive subtype is due to the dysregulation of CTNNB1, PTEN and JAK2. This work suggests that moderate and severe OED that harbor the non-cytotoxic or non-immune reactive subtype are likely to progress to cancer. Overall, we showed that distinct immune responses are present in high-risk OPMD, and revealed targetable pathways that could lead to potential new approaches for non-surgical management of OED. Frontiers Media S.A. 2022-09-02 /pmc/articles/PMC9479061/ /pubmed/36119104 http://dx.doi.org/10.3389/fimmu.2022.954567 Text en Copyright © 2022 Gan, Lee, Lau, Kallarakkal, Zaini, Lye, Zain, Sathasivam, Yeong, Savelyeva, Thomas, Ottensmeier, Ariffin, Cheong and Lim https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Gan, Chai Phei
Lee, Bernard Kok Bang
Lau, Shin Hin
Kallarakkal, Thomas George
Zaini, Zuraiza Mohamad
Lye, Bryan Kit Weng
Zain, Rosnah Binti
Sathasivam, Hans Prakash
Yeong, Joe Poh Sheng
Savelyeva, Natalia
Thomas, Gareth
Ottensmeier, Christian H.
Ariffin, Hany
Cheong, Sok Ching
Lim, Kue Peng
Transcriptional analysis highlights three distinct immune profiles of high-risk oral epithelial dysplasia
title Transcriptional analysis highlights three distinct immune profiles of high-risk oral epithelial dysplasia
title_full Transcriptional analysis highlights three distinct immune profiles of high-risk oral epithelial dysplasia
title_fullStr Transcriptional analysis highlights three distinct immune profiles of high-risk oral epithelial dysplasia
title_full_unstemmed Transcriptional analysis highlights three distinct immune profiles of high-risk oral epithelial dysplasia
title_short Transcriptional analysis highlights three distinct immune profiles of high-risk oral epithelial dysplasia
title_sort transcriptional analysis highlights three distinct immune profiles of high-risk oral epithelial dysplasia
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9479061/
https://www.ncbi.nlm.nih.gov/pubmed/36119104
http://dx.doi.org/10.3389/fimmu.2022.954567
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