Cargando…
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...
Autores principales: | , , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1784790706477334528 |
---|---|
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. |
format | Online Article Text |
id | pubmed-9479061 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT ganchaiphei transcriptionalanalysishighlightsthreedistinctimmuneprofilesofhighriskoralepithelialdysplasia AT leebernardkokbang transcriptionalanalysishighlightsthreedistinctimmuneprofilesofhighriskoralepithelialdysplasia AT laushinhin transcriptionalanalysishighlightsthreedistinctimmuneprofilesofhighriskoralepithelialdysplasia AT kallarakkalthomasgeorge transcriptionalanalysishighlightsthreedistinctimmuneprofilesofhighriskoralepithelialdysplasia AT zainizuraizamohamad transcriptionalanalysishighlightsthreedistinctimmuneprofilesofhighriskoralepithelialdysplasia AT lyebryankitweng transcriptionalanalysishighlightsthreedistinctimmuneprofilesofhighriskoralepithelialdysplasia AT zainrosnahbinti transcriptionalanalysishighlightsthreedistinctimmuneprofilesofhighriskoralepithelialdysplasia AT sathasivamhansprakash transcriptionalanalysishighlightsthreedistinctimmuneprofilesofhighriskoralepithelialdysplasia AT yeongjoepohsheng transcriptionalanalysishighlightsthreedistinctimmuneprofilesofhighriskoralepithelialdysplasia AT savelyevanatalia transcriptionalanalysishighlightsthreedistinctimmuneprofilesofhighriskoralepithelialdysplasia AT thomasgareth transcriptionalanalysishighlightsthreedistinctimmuneprofilesofhighriskoralepithelialdysplasia AT ottensmeierchristianh transcriptionalanalysishighlightsthreedistinctimmuneprofilesofhighriskoralepithelialdysplasia AT ariffinhany transcriptionalanalysishighlightsthreedistinctimmuneprofilesofhighriskoralepithelialdysplasia AT cheongsokching transcriptionalanalysishighlightsthreedistinctimmuneprofilesofhighriskoralepithelialdysplasia AT limkuepeng transcriptionalanalysishighlightsthreedistinctimmuneprofilesofhighriskoralepithelialdysplasia |