Characterization of the Immunomic Profile of Head and Neck Cancer

描述(申请人提供)：在全球范围内，头颈部鳞状细胞癌(HNSCC)是最常见的癌症之一，影响约50万人。仅在美国，口腔癌每年导致的死亡人数就超过了宫颈癌、黑色素瘤或淋巴瘤。5年存活率不到50%，这一预后比乳腺癌或黑色素瘤更差。HNSCC的不良预后是由于发现较晚；要么是由于后侧舌的可视化差；要么是由于临床表现为无害的红色或白色，很容易与炎症或刺激相混淆。晚期HNSCC患者接受高度侵袭性的手术和放射治疗，导致舌头和唾液腺等组织丢失。幸存的患者必须面对巨大的身体和情感挑战，包括面部毁容、进食和语言障碍以及糟糕的生活质量。虽然，很大比例的晚期肿瘤对化疗/放疗(非手术)有反应，但没有预测治疗反应的参数。需要一种高通量的HNSCC筛查方法。这些知识的发展将加强对HNSCC的检测，提高患者的生存和生活质量。癌症患者会产生针对肿瘤特异性抗原的抗体，这表明这些自身抗体可能具有诊断和预后价值。初步数据表明，可以确定HNSCC的特异性抗体库。确定HNSCC中产生的针对肿瘤抗原的全部抗体库将导致高度特异和灵敏的多重检测HNSCC。因此，这项拟议研究的中心假设是，内源性免疫系统可以被用作检测HNSCC的生物“传感器”。目的是开发HNSCC噬菌体展示文库，并利用噬菌体免疫组学微阵列表征HNSCC的“体液特征”。 与公共卫生相关：HNSCC预后较差的原因是发现较晚；要么是因为舌后部的可视化能力差；要么是因为临床表现为无害的红色或白色，很容易与刺激相混淆。目前的口腔癌筛查测试不充分，不具特异性，而且缺乏可及性。癌症患者会产生针对肿瘤特异性抗原的抗体，这表明这些自身抗体可能具有诊断和预后价值。因此，内源性免疫系统可以被用作HNSCC早期检测的生物“传感器”。这将通过开发HNSCC噬菌体展示文库和免疫组学微阵列并使用这些系统来表征HNSCC的体液特征来实现。这将为HNSCC的早期检测提供高度特异和敏感的多重检测方法。

DESCRIPTION (provided by applicant): Globally, head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers, and affects ~500,000 individuals. In the US alone, oral cancer accounts for more deaths annually than cervical cancer, melanoma, or lymphoma. The 5-year survival rate is less than 50%, a prognosis that is poorer than breast cancer or melanoma. The poor prognosis of HNSCC is due to late detection; either due to poor visualization as in the posterior-lateral tongue; or due to an innocuous red or white clinical appearance that is easily confused with inflammation or irritation. Patients with late stage HNSCC receive highly aggressive surgical and radiation treatment, leading to loss of tissues such as the tongue and salivary glands. The surviving patient must confront monumental physical and emotional challenges that include facial disfiguration, feeding and speech impediments and poor quality of life. Although, a significant proportion of late stage tumors would have responded to chemotherapy/radiation (no surgery), no predictive parameters of treatment response exist. What is needed is a high throughput screening assay for HNSCC. Development of such knowledge will enhance detection of HNSCC and improve patient survival and quality of life. Patients with cancer produce antibodies against tumor-specific antigens, suggesting that these autoantibodies may have diagnostic and prognostic value. Preliminary data here indicate that a specific antibody repertoire can be identified for HNSCC. Defining the entire antibody repertoire produced against tumor antigens in HNSCC will lead to highly specific and sensitive multiplexed assays for detection of HNSCC. Thus, the central hypothesis of the proposed research is that the endogenous immune system can be harnessed as a biological "sensor" for detection of HNSCC. The objectives are to develop a HNSCC phage display library and to characterize the "humoral signature" for HNSCC using phage immunomic microarrays. PUBLIC HEALTH RELEVANCE: The poor prognosis of HNSCC is attributable to late detection; either due to poor visualization as in the posterior tongue; or to an innocuous red or white clinical appearance easily confused with irritation. Current oral cancer screening tests are inadequate, not specific, and poorly accessed. Patients with cancer produce antibodies against tumor-specific antigens, suggesting that these autoantibodies may have diagnostic and prognostic value. Thus, the endogenous immune system can be harnessed as a biological "sensor" for early detection of HNSCC. This will be accomplished by developing a HNSCC phage display library and immunomic microarrays and using these systems to characterize the humoral signature for HNSCC. This will lead to highly specific and sensitive multiplexed assays for early detection of HNSCC.