Developing Imaging Biomarkers of Oral Squamous Cell Carcinoma Response to Immunotherapy

口腔鳞状细胞癌（OSCC）是一种侵袭性恶性肿瘤，通常在晚期被诊断出来， 在患者中的阶段，因此与预后不良有关。最近，免疫检查点抑制剂 已获得监管机构批准用于晚期OSCC患者。尽管一些口腔鳞状细胞癌患者表现出 免疫疗法的反应显著，但总体反应率仍然很低。识别早期非侵入性 因此，免疫功效的生物标志物可能对患者选择具有显著影响。在这 关于这一点，我们的实验室一直在研究超声（US）与空间共配准的潜力。 光声成像（派）监测OSCC进展，并可能预测对免疫治疗的反应。 使用一种新的原位免疫活性OSCC模型（RP-MOC 1），我们已经证明了 US-PAI用于监测OSCC进展过程中的功能性血管变化。在初步研究中，我们还 观察到早期血管对免疫治疗的反应之间存在显著相关性， US-PAI和长期治疗结局。基于这些令人兴奋的初步观察，我们的 假设通过US-PAI检测对免疫治疗的早期血管反应可以作为 OSCC进展和免疫功效。为了验证这一假设，我们将研究肿瘤血管分布和T细胞分布变化之间的时空相关性（目的1），并评估肿瘤血管分布和T细胞分布变化之间的时空相关性。 基于US-PAI的血流动力学反应对免疫治疗的特异性OSCC反应（目的2）。 成功完成拟议的研究可以进一步开发US-PAI作为一种新的药物， 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.