Aptamer specific for myeloid derived suppressor cells for the diagnosis of head and neck cancer from the oral rinse

发展灵敏和特异的诊断方法以早期发现头颈癌。 仍然是一个未得到满足的医疗需求。大多数正在开发的分析方法依赖于一种肿瘤细胞生物标记物，这种生物标记物通常存在于 仅有一定比例的肿瘤细胞和/或部分头颈部鳞状细胞癌患者 (HNSCC)。因此，单个患者和不同患者之间肿瘤细胞的内在异质性 事实限制了这些分析的灵敏度。为了解决这个问题，我们建议监控HNSCC 使用识别肿瘤浸润性髓系细胞的RNA适配子在口腔含漱液中存在。这些细胞 在肿瘤发生的早期，大量地侵袭病变，参与肿瘤的发生和发展 进展，并预测HNSCC的复发。此外，这些细胞在肿瘤中会迅速更新。 并在肿瘤微环境和附近的液体中释放它们的内容。 我们鉴定了四种识别髓系抑制细胞和巨噬细胞的RNA适配子。 对所有患者的HNSCC肿瘤而不是血液或健康组织中的髓样组织进行评估。 此外，我们的可行性和原则性实验证明，这些适配子可能会区分 头颈癌患者与健康献血者的口腔含漱液。我们建议测试一下 假设用于线性表面等离子体共振(LSPR)实验的MDSC特异性适配子可以 从口腔含漱液中检测HNSCC具有很高的敏感性和特异性。我们将首先使用以下方法优化化验 样品已经存入我们机构。然后，我们将进行一项前瞻性临床研究，在该研究中，我们将测试 150例经活检证实的HNSCC患者(所有阶段，所有部位)和150名年龄匹配的健康人的口腔漱口水 捐赠者。特别是，我们将并排比较以LSPR为配体的LSPR检测的敏感性和特异性 要么是我们的MDSC特异性适配子，要么是针对CD44的抗体，CD44是与HNSCC密切相关的标志 正在开发用于从口腔漱口水诊断HNSCC的方法，结果令人振奋。 总之，我们提出了一种新的方法来早期诊断HNSCC，这是一种通常只被诊断出来的疾病 晚期预后差，治疗发病率高。我们的假设应该是 是的，我们预计基于MDSC存在的检测可能有助于在早期发现这种恶性肿瘤 治疗最有效、侵入性最小的阶段。

The development of sensitive and specific diagnostic assays for the early detection of Head and Neck Cancer is still an unmet medical need. Most assays being developed rely on a neoplastic cell biomarker often present in only a proportion of neoplastic cells and/or a subset of patients with Head and Neck Squamous Cell carcinoma (HNSCC). As such, the intrinsic heterogeneity of the neoplastic cell within a single patient and across patients de facto limits the sensitivity of these assays. To overcome this problem, we propose to monitor HNSCC presence in the oral rinse using RNA aptamers that recognize tumor-infiltrating myeloid cells. These cells infiltrate the lesion in high numbers and early during tumorigenesis, participate in tumor initiation and progression, and predict recurrence in HNSCC. Additionally, these cells are quickly renewed in the tumor microenvironment and release their content in the tumor microenvironment and nearby fluid. We identified four RNA aptamers that recognize myeloid derived suppressor cells and macrophages in the HNSCC tumor but not the myeloid counterparts in the blood or healthy tissues in all patients evaluated. Additionally, our feasibility and proof of principle experiments indicate that these aptamers might discriminate oral rinses of patients with head and neck cancers from those of healthy donors. We propose to test the hypothesis that MDSC-specific aptamers used in linear surface plasmon resonance (LSPR) experiments can detect HNSCC from the oral rinse with high sensitivity and specificity. We will first optimize the assay using samples already banked in our institution. Then, we will perform a prospective clinical study in which we will test oral rinses from 150 patients with biopsy-proven HNSCC (all stage, all sites) and 150 age-matched healthy donors. In particular, we will compare side-by-side the sensitivity and specificity of LSPR assays using as ligand either our MDSC specific aptamers or an antibody against CD44, a marker strongly associated with HNSCC that is being developed for HNSCC diagnosis from the oral rinse with promising results. In summary, we propose a novel approach for the early diagnosis of HNSCC, a disease often diagnosed only in advanced stages when the prognosis is poor, and the treatment morbidity is high. Should our hypothesis be true, we anticipate that assays based on the presence of MDSC may aid in detecting this malignancy at earlier stages when treatments are most effective and less invasive.