Developing Imaging Biomarkers of Oral Squamous Cell Carcinoma Response to Immunotherapy

口腔鳞状细胞癌(OSCC)是一种侵袭性的恶性肿瘤，通常被诊断为晚期。 在患者中分期，因此与预后不良有关。最近，免疫检查点抑制剂 已获得监管部门对晚期口腔鳞癌患者的批准。尽管一些口腔鳞癌患者表现出 免疫治疗反应显著，总体应答率仍较低。识别早期的非侵入性 因此，免疫治疗效果的生物标志物可能会对患者的选择产生重大影响。在这 在这方面，我们的实验室一直在研究超声(US)与空间联合注册的潜力 光声成像(PAI)用于监测口腔鳞癌的进展，并有可能预测免疫治疗的反应。 使用一种新的、原位的、免疫活性的口腔鳞癌模型(RP-MOC1)，我们已经证明了 US-PAI用于监测口腔鳞癌进展过程中功能性血管的变化。在初步研究中，我们还 观察发现，早期血管对免疫治疗的反应与 US-PAI与长期治疗结果。基于这些令人兴奋的初步观察，我们的 US-PAI检测到早期血管对免疫治疗的反应可作为一种生物标志物 口腔鳞癌进展与免疫治疗疗效的关系。为了验证这一假设，我们将检验肿瘤血管变化和T细胞特征之间的时空相关性(目标1)，并评估其能力 基于US-PAI的血流动力学反应预测口腔鳞癌对免疫治疗的反应(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 指导患者选择、监测免疫治疗和预测结果的方法。

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.