Clare Prarthna, Al-Fatyan Farah, Risheh Badri, Nellany Kristine, Ward Frank James, Abu-Eid Rasha
Institute of Dentistry, School of Medicine, Medical Sciences & Nutrition, University of Aberdeen, Aberdeen AB25 2ZR, UK.
Institute of Medical Sciences, School of Medicine, Medical Sciences & Nutrition, University of Aberdeen, Aberdeen AB25 2ZR, UK.
Cancers (Basel). 2023 Mar 10;15(6):1696. doi: 10.3390/cancers15061696.
: 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. 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. 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. 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.
头颈部癌症（HNC）死亡率很高，晚期诊断仍然是影响患者生存的最重要因素。因此，确定有助于早期检测和预测疾病进展的标志物势在必行。HNC通过包括免疫检查点在内的不同机制逃避免疫系统。细胞毒性T淋巴细胞相关蛋白4（CTLA-4）是一种免疫检查点受体，可下调抗肿瘤免疫反应，有证据表明其与HNC有关。研究较少的可变剪接可溶性异构体（sCTLA-4）也发挥免疫抑制作用，促成免疫逃逸。我们对正常、潜在恶性以及恶性口腔和口咽组织中的sCTLA-4进行定量，以阐明其在肿瘤发生中的任何作用，并确定其作为诊断和患者分层生物标志物的潜力。对正常、低级别和高级别上皮发育异常以及口腔和口咽鳞状细胞癌活检组织进行sCTLA-4选择性染色，并使用图像分析软件QuPath进行定量。观察到不同的sCTLA-4染色模式，其中正常上皮sCTLA-4表达与角质形成细胞分化相关，而在发育异常和肿瘤组织中观察到强度和定位方面的表达破坏。我们的数据表明sCTLA-4在上皮细胞分化和增殖中具有额外的、以前未知的作用。此外，我们的研究结果表明sCTLA-4有潜力作为预测疾病进展和HNC靶向治疗患者分层的生物标志物。
