Developing Imaging Biomarkers of Oral Squamous Cell Carcinoma Response to Immunotherapy

开发口腔鳞状细胞癌对免疫治疗反应的成像生物标志物

• 批准号: 10314822
• 负责人: Celia DeJohn
• 金额: $ 3.17万
• 依托单位: ROSWELL PARK CANCER INSTITUTE CORP
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10314822
• 关键词: 3-Dimensional; 3D ultrasound; Address; Biological Markers; Blood Vessels; CD8B1 gene; Cancer Patient; Cells; Clinical; Contrast Media; Data; Development; Diagnosis; Evaluation; Exhibits; Flow Cytometry; Goals; Hemoglobin; Histological Techniques; Human; Hybrids; Hypoxia; Image; Imaging Techniques; Immune; Immune checkpoint inhibitor; Immunocompetent; Immunohistochemistry; Immunologic Markers; Immunooncology; Immunotherapeutic agent; Immunotherapy; In complete remission; Ionizing radiation; Knowledge; Laboratories; Magnetic Resonance Imaging; Malignant Neoplasms; Maps; Measures; Methods; Minority; Modeling; Monitor; Morbidity - disease rate; Mutation; Nivolumab; Optics; Oxygen; PECAM1 gene; Patient Selection; Patient-Focused Outcomes; Patients; Play; Positron-Emission Tomography; Prognosis; Progressive Disease; Property; Radiolabeled; Role; Series; T-Lymphocyte; Testing; Time; Tissues; Toxic effect; Tracer; Treatment outcome; Ultrasonography; Validation; Vascular Endothelial Growth Factors; Water; X-Ray Computed Tomography; base; checkpoint therapy; chromophore; cohort; hemodynamics; imaging biomarker; imaging modality; immune checkpoint blockade; in vivo; malignant mouth neoplasm; mortality; mouse model; mouth squamous cell carcinoma; neoantigens; non-invasive imaging; novel; novel strategies; outcome prediction; partial response; pembrolizumab; photoacoustic imaging; preclinical study; predicting response; pressure; prognostic; prognostic value; programmed cell death ligand 1; programmed cell death protein 1; prospective; responders and non-responders; response; response biomarker; sound; spatiotemporal; success; tumor; tumor heterogeneity; tumor microenvironment; tumor progression

Oral squamous cell carcinomas (OSCC) are aggressive malignancies that are often diagnosed at advanced stages in patients and therefore associated with a poor prognosis. Recently, immune checkpoint inhibitors have received regulatory approval for advanced OSCC patients. Although some OSCC patients exhibit remarkable response to immunotherapy, overall response rates remain low. Identifying an early noninvasive biomarker of immunotherapeutic efficacy could therefore have a significant impact in patient selection. In this regard, our laboratory has been investigating the potential of ultrasound (US) with spatially co-registered photoacoustic imaging (PAI) to monitor OSCC progression and potentially predict response to immunotherapy. Using a novel, orthotopic, immunocompetent model of OSCC (RP-MOC1) we have demonstrated the ability of US-PAI to monitor functional vascular changes during OSCC progression. In preliminary studies, we have also observed observed a significant association between early vascular response to immunotherapy detected by US-PAI and long-term treatment outcomes. Based on these exciting preliminary observations, it is our hypothesis that early vascular response to immunotherapy detected by US-PAI can serve as a biomarker of OSCC progression and immunotherapeutic efficacy. To test this hypothesis, we will examine the spatio-temporal correlation between changes in tumor vascularity and T-cell profiles (Aim 1) and evaluate the ability of US-PAI based hemodynamic response to prognosticate OSCC response to immunotherapy (Aim 2). Successful completion of the proposed studies could enable further development of US-PAI as a novel approach to guide patient selection, monitor immunotherapy, and predict outcomes.

口腔鳞状细胞癌 (OSCC) 是一种侵袭性恶性肿瘤，通常在晚期才被诊断出来。 患者的分期，因此与不良预后相关。最近，免疫检查点抑制剂 已获得针对晚期 OSCC 患者的监管批准。尽管一些 OSCC 患者表现出 对免疫疗法的反应显着，但总体反应率仍然较低。识别早期非侵入性 因此，免疫治疗功效的生物标志物可能对患者选择产生重大影响。在这个 就此而言，我们的实验室一直在研究超声波（美国）与空间共同配准的潜力 光声成像（PAI）用于监测 OSCC 进展并可能预测对免疫治疗的反应。 使用新型原位免疫活性 OSCC 模型 (RP-MOC1)，我们证明了 US-PAI 用于监测 OSCC 进展期间的功能性血管变化。在前期研究中，我们还 观察到早期血管对免疫治疗的反应之间存在显着关联 US-PAI 和长期治疗结果。基于这些令人兴奋的初步观察，我们 假设 US-PAI 检测到的早期血管对免疫治疗的反应可以作为免疫治疗的生物标志物 口腔鳞癌的进展和免疫治疗效果。为了检验这一假设，我们将检查肿瘤血管分布和 T 细胞分布变化之间的时空相关性（目标 1）并评估能力 基于 US-PAI 的血流动力学反应来预测 OSCC 对免疫治疗的反应（目标 2）。 成功完成拟议的研究可以使 US-PAI 进一步发展为一种新型药物 指导患者选择、监测免疫治疗和预测结果的方法。