FAST-FNA immune cell profiling in HNSCC

HNSCC 中的 FAST-FNA 免疫细胞分析

• 批准号: 10578849
• 负责人: Sara Isabel Pai
• 金额: $ 65.73万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-01-26 至 2025-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10578849
• 关键词: Address; Antibodies; Archives; Artificial Intelligence; B-Lymphocytes; Biological Markers; Biopsy; Biopsy Specimen; Cells; Certification; Chemistry; Clinical; Clinical Laboratory Improvement Amendments; Consumption; Core Biopsy; Diagnostic; Emerging Technologies; Engineering; Evaluation; Evolution; Fine needle aspiration biopsy; Fresh Tissue; Goals; Head and Neck Squamous Cell Carcinoma; Human; Image Guided Biopsy; Immune; Immune response; Immunotherapeutic agent; Immunotherapy; Laboratories; Malignant Neoplasms; Methods; Modification; Morbidity - disease rate; Needles; Pathologist; Patients; Physiologic Monitoring; Quality Control; Recurrence; Research; Sampling; Sedation procedure; Site; Specimen; Stains; System; T-Lymphocyte; Technology; Testing; Time; Tissue Harvesting; Tissues; Training; Translating; Treatment Efficacy; Treatment Protocols; United States Food and Drug Administration; Validation; anti-PD-1; biomarker discovery; biomarker validation; cancer cell; chemotherapy; clinical application; clinical predictors; companion diagnostics; cost; experimental study; innovation; molecular marker; mouse model; novel; predictive marker; programmed cell death ligand 1; prospective; response; response biomarker; therapy outcome; translational goal; tumor; tumor microenvironment

Currently, the single best predictive biomarker of response to anti-PD1 monotherapy is PD-L1 expression as assessed by immunohistochemical staining of archived or fresh tissue. Current workflows for PD-L1 assessment in tissue are labor and time consuming, are not infallible (inconclusive results in a fraction of image guided biopsies) and are associated with morbidity and are thus rarely performed serially. Rapid on site assessment of cellular, rather than tissue, specimens obtained through fine needle aspiration (FNA) could not only circumvent these bottlenecks but also enable more comprehensive and serial profiling of the tumor microenvironment to obtain the most up-to-date information of a rapidly changing microenvironment during tumor evolution and therapy. The goal of this project is to further develop and validate the new FAST-FNA technology for rapid biomarker discovery and validation in HNSCCs. There are two main aims. In aim 1 we will develop and validate existing and new biomarkers in FNA samples of HNSCC patients (n=100). Specifically we will I) develop and validate new predictive immunotherapeutic biomarkers and ii to determine how well the new FAST-FNA scores correlate with the CPS scores of PD-L1. The goal of the second aim is to translate the above FAST-FNA technology to serial FNA analyses in HNSCC patients receiving anti-PD1 immunotherapy (with or without chemotherapy; n=100). FNA sampling will be performed pre- and on-treatment in order to capture changes in the tumor microenvironment. As the HNSCC field shifts toward increased biomarker testing, we find an unmet clinical need to develop advanced cellular diagnostics in HNSCCs, which will facilitate rapid biomarker analysis, guide therapies and provide “real time” assessment of clinical response.

目前，抗PD 1单药治疗应答的单一最佳预测生物标志物是PD-L1表达， 通过存档或新鲜组织的免疫组织化学染色进行评估。PD-L1的当前工作流程 组织中的评估是费力和耗时的，并不是绝对可靠的（在一小部分组织中不确定的结果）。 图像引导的活组织检查）并且与发病率相关，因此很少连续进行。快速现场 通过细针穿刺（FNA）获得的细胞而非组织样本的评估不能 不仅绕过了这些瓶颈，而且还能够对肿瘤进行更全面和连续的分析， 微环境，以获得快速变化的微环境的最新信息， 肿瘤演变和治疗。本项目的目标是进一步开发和验证新的FAST-FNA 用于HNSCC中快速生物标志物发现和验证的技术。有两个主要目标。在目标1中， 在HNSCC患者的FNA样品中开发和验证现有的和新的生物标志物（n=100）。另外还 I）开发和验证新的预测性免疫生物标志物，ii）确定新的 FAST-FNA评分与PD-L1的CPS评分相关。第二个目标的目标是翻译 上述FAST-FNA技术用于接受抗PD 1免疫治疗的HNSCC患者的系列FNA分析 (with或未化疗; n=100）。将在治疗前和治疗期间进行FNA采样，以 捕捉肿瘤微环境的变化。随着HNSCC领域向增加的生物标志物转移， 测试，我们发现一个未满足的临床需要，以发展先进的细胞诊断HNSCCs，这将 促进快速生物标志物分析，指导治疗，并提供临床反应的“真实的时间”评估。