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

基本信息

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
项目类别：
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

项目摘要

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.

口服鳞状细胞癌（OSCC）是侵略性恶性肿瘤，通常在高级时被诊断出患者的阶段，因此与预后不良有关。最近，免疫检查点抑制剂已获得高级OSCC患者的监管批准。尽管一些OSCC患者表现出对免疫疗法的显着反应，总体反应率仍然很低。识别早期无创的因此，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。在这个考虑到，我们的实验室一直在研究超声（US）的潜力光声成像（PAI）以监测OSCC进展并有可能预测对免疫疗法的反应。使用新型的OSCC的原位，免疫功能模型（RP-MOC1），我们证明了能力 US-PAI监测OSCC进展过程中功能性血管变化。在初步研究中，我们也观察到观察到的早期血管反应对由美国赛和长期治疗结果。基于这些令人兴奋的初步观察，这是我们的假设US-PAI检测到的免疫疗法的早期血管反应可以作为生物标志物 OSCC的进展和免疫治疗功效。为了检验这一假设，我们将研究肿瘤血管变化和T细胞谱之间的时空相关性（AIM 1），并评估能力基于US-PAI的对预后OSCC对免疫疗法的反应的血液动力学反应（AIM 2）。成功完成拟议的研究可以使US-PAI作为新颖的进一步发展指导患者选择，监测免疫疗法并预测结果的方法。