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

Gan, Chai Phei and Lee, Bernard Kok Bang and Lau, Shin Hin and Kallarakkal, Thomas George and Zaini, Zuraiza Mohamad and Lye, Bryan Kit Weng and Zain, Rosnah Binti and Sathasivam, Hans Prakash and Yeong, Joe Poh Sheng and Savelyeva, Natalia and Thomas, Gareth and Ottensmeier, Christian H. and Ariffin, Hany and Cheong, Sok Ching and Lim, Kue Peng (2022) Transcriptional analysis highlights three distinct immune profiles of high-risk oral epithelial dysplasia. Frontiers in Microbiology, 13. ISSN 1664-302X, DOI

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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.

Item Type: Article
Funders: Global Challenges Research Fund of the Medical Research Council, UK, Cancer Research Malaysia [MR/P024351/1]
Uncontrolled Keywords: Immune signature; Non-immune reactive; Immune cytotoxic; Oral premalignant lesion; Oral epithelial dysplasia; Oral potentially malignant disorder
Subjects: R Medicine
Divisions: Faculty of Medicine
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 07 Sep 2023 03:23
Last Modified: 07 Sep 2023 03:23

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