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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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.954567/full |
| _version_ | 1811184733421305856 |
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| author | Chai Phei Gan Chai Phei Gan Bernard Kok Bang Lee Shin Hin Lau Thomas George Kallarakkal Thomas George Kallarakkal Zuraiza Mohamad Zaini Bryan Kit Weng Lye Rosnah Binti Zain Rosnah Binti Zain Hans Prakash Sathasivam Joe Poh Sheng Yeong Joe Poh Sheng Yeong Natalia Savelyeva Gareth Thomas Christian H. Ottensmeier Christian H. Ottensmeier Hany Ariffin Sok Ching Cheong Sok Ching Cheong Kue Peng Lim |
| author_facet | Chai Phei Gan Chai Phei Gan Bernard Kok Bang Lee Shin Hin Lau Thomas George Kallarakkal Thomas George Kallarakkal Zuraiza Mohamad Zaini Bryan Kit Weng Lye Rosnah Binti Zain Rosnah Binti Zain Hans Prakash Sathasivam Joe Poh Sheng Yeong Joe Poh Sheng Yeong Natalia Savelyeva Gareth Thomas Christian H. Ottensmeier Christian H. Ottensmeier Hany Ariffin Sok Ching Cheong Sok Ching Cheong Kue Peng Lim |
| author_sort | Chai Phei Gan |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-11T13:18:31Z |
| format | Article |
| id | doaj.art-c922d4cc37a2451ca4be9978be7c9737 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-11T13:18:31Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-c922d4cc37a2451ca4be9978be7c97372022-12-22T04:22:20ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-09-011310.3389/fimmu.2022.954567954567Transcriptional analysis highlights three distinct immune profiles of high-risk oral epithelial dysplasiaChai Phei Gan0Chai Phei Gan1Bernard Kok Bang Lee2Shin Hin Lau3Thomas George Kallarakkal4Thomas George Kallarakkal5Zuraiza Mohamad Zaini6Bryan Kit Weng Lye7Rosnah Binti Zain8Rosnah Binti Zain9Hans Prakash Sathasivam10Joe Poh Sheng Yeong11Joe Poh Sheng Yeong12Natalia Savelyeva13Gareth Thomas14Christian H. Ottensmeier15Christian H. Ottensmeier16Hany Ariffin17Sok Ching Cheong18Sok Ching Cheong19Kue Peng Lim20Cancer Immunology and Immunotherapy Unit, Cancer Research Malaysia, Subang Jaya, MalaysiaDepartment of Paediatrics, Faculty of Medicine, University of Malaya, Kuala Lumpur, MalaysiaCancer Immunology and Immunotherapy Unit, Cancer Research Malaysia, Subang Jaya, MalaysiaCancer Research Center, Institute for Medical Research, National Institutes of Health, Ministry of Health Malaysia, Shah Alam, MalaysiaDepartment of Oral and Maxillofacial Clinical Sciences, Faculty of Dentistry, University of Malaya, Kuala Lumpur, MalaysiaOral Cancer Research and Coordinating Center, Faculty of Dentistry, University of Malaya, Kuala Lumpur, MalaysiaDepartment of Oral and Maxillofacial Clinical Sciences, Faculty of Dentistry, University of Malaya, Kuala Lumpur, MalaysiaCancer Immunology and Immunotherapy Unit, Cancer Research Malaysia, Subang Jaya, MalaysiaOral Cancer Research and Coordinating Center, Faculty of Dentistry, University of Malaya, Kuala Lumpur, MalaysiaFaculty of Dentistry, Malaysian Allied Health Sciences Academy (MAHSA) University, Jenjarom, MalaysiaCancer Research Center, Institute for Medical Research, National Institutes of Health, Ministry of Health Malaysia, Shah Alam, MalaysiaIntegrative Biology for Theranostics, Institute of Molecular Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore, SingaporeDepartment of Anatomical Pathology, Singapore General Hospital, Singapore, SingaporeHead and Neck Center, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdom0Cancer Sciences, University of Southampton, Southampton, United KingdomHead and Neck Center, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdom0Cancer Sciences, University of Southampton, Southampton, United KingdomDepartment of Paediatrics, Faculty of Medicine, University of Malaya, Kuala Lumpur, MalaysiaCancer Immunology and Immunotherapy Unit, Cancer Research Malaysia, Subang Jaya, MalaysiaDepartment of Oral and Maxillofacial Clinical Sciences, Faculty of Dentistry, University of Malaya, Kuala Lumpur, MalaysiaCancer Immunology and Immunotherapy Unit, Cancer Research Malaysia, Subang Jaya, MalaysiaOral 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.https://www.frontiersin.org/articles/10.3389/fimmu.2022.954567/fullimmune signaturenon-immune reactiveimmune cytotoxicoral premalignant lesionoral epithelial dysplasiaoral potentially malignant disorder |
| spellingShingle | Chai Phei Gan Chai Phei Gan Bernard Kok Bang Lee Shin Hin Lau Thomas George Kallarakkal Thomas George Kallarakkal Zuraiza Mohamad Zaini Bryan Kit Weng Lye Rosnah Binti Zain Rosnah Binti Zain Hans Prakash Sathasivam Joe Poh Sheng Yeong Joe Poh Sheng Yeong Natalia Savelyeva Gareth Thomas Christian H. Ottensmeier Christian H. Ottensmeier Hany Ariffin Sok Ching Cheong Sok Ching Cheong Kue Peng Lim Transcriptional analysis highlights three distinct immune profiles of high-risk oral epithelial dysplasia Frontiers in Immunology immune signature non-immune reactive immune cytotoxic oral premalignant lesion oral epithelial dysplasia oral potentially malignant disorder |
| 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 | immune signature non-immune reactive immune cytotoxic oral premalignant lesion oral epithelial dysplasia oral potentially malignant disorder |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.954567/full |
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