A Novel Role for the Soluble Isoform of CTLA-4 in Normal, Dysplastic and Neoplastic Oral and Oropharyngeal Epithelia.
Simple Summary: Head and neck cancers have a poor prognosis mainly attributed to late diagnosis when a cure is not possible. Markers that are capable of predicting cancerous changes at an early stage are needed. Here, we quantified the soluble isoform of CTLA-4 (sCTLA-4), a molecule usually describe...
| Publicado en: | Cancers Vol. 15; no. 6; pp. 1696 - 1712 |
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| Autores principales: | , , , , , |
| Formato: | pictorial research tables/charts Journal Article |
| Publicado: |
MDPI
Mar2023
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=162751095&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 162751095 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 20726694 B74B jtl: Cancers issn: 20726694 maglogo: N pubinfo: dt: Mar2023 vid: 15 iid: 6 pid: 97109 pub: MDPI artinfo: ui: 162751095 162751095 162751095 10.3390/cancers15061696 162751095 ppf: 1696 ppct: 16 formats: tig: atl: A Novel Role for the Soluble Isoform of CTLA-4 in Normal, Dysplastic and Neoplastic Oral and Oropharyngeal Epithelia. aug: au: Clare, Prarthna Al-Fatyan, Farah Risheh, Badri Nellany, Kristine Ward, Frank James Abu-Eid, Rasha affil: Institute of Dentistry, School of Medicine, Medical Sciences & Nutrition, University of Aberdeen, Aberdeen AB25 2ZR, UK sug: subj: Head and Neck Neoplasms Drug Therapy Immunotherapy Methods T Lymphocytes Human Tumor Markers, Biological Biopsy Methods Keratinocytes Immunosuppression Neoplasms, Glandular and Epithelial Fluorescent Antibody Technique Immunohistochemistry Staining and Labeling T-Tests Kruskal-Wallis Test Analysis of Variance Post Hoc Analysis Mann-Whitney U Test Descriptive Statistics Funding Source ab: Simple Summary: Head and neck cancers have a poor prognosis mainly attributed to late diagnosis when a cure is not possible. Markers that are capable of predicting cancerous changes at an early stage are needed. Here, we quantified the soluble isoform of CTLA-4 (sCTLA-4), a molecule usually described for its immune function, in normal, potentially malignant and malignant oral and oropharyngeal epithelial samples. We report a distinct sCTLA-4 staning pattern and distribution in normal samples indicative of a new role for this molecule in epithelial cell growth and development. We also describe significant changes in sCTLA-4 staining in potentially malignant and malignant samples, suggestiong the potential of sCTLA-4 as a predictor of disease progression. Background: Head and neck cancer (HNC) has a high mortality rate, with late diagnosis remaining the most important factor affecting patient survival. Therefore, it is imperative to identify markers that aid in early detection and prediction of disease progression. HNCs evade the immune system by different mechanisms, including immune checkpoints. Cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) is an immune checkpoint receptor that downregulates anti-tumour immune responses, with evidence of involvement in HNC. The less studied, alternatively spliced, soluble isoform (sCTLA-4) also plays an immunosuppressive role that contributes to immune escape. We quantified sCTLA-4 in normal, potentially malignant, and malignant oral and oropharyngeal tissues to elucidate any role in tumourigenesis and identify its potential as a biomarker for diagnosis and patient stratification. Methods: Normal, low- and high-grade epithelial dysplasia, and squamous cell carcinoma oral and oropharyngeal biopsies were selectively stained for sCTLA-4 and quantified using the image analysis software QuPath. Results: Distinct sCTLA-4 staining patterns were observed, in which normal epithelial sCTLA-4 expression correlated with keratinocyte differentiation, while disrupted expression, both in intensity and localisation, was observed in dysplastic and neoplastic tissues. Conclusions: Our data indicate an additional, previously unknown role for sCTLA-4 in epithelial cell differentiation and proliferation. Furthermore, our findings suggest the potential of sCTLA-4 as a biomarker for predicting disease progression and patient stratification for targeted HNC therapies. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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