Xu Yan, Mcmillan Alexandra, Gupta Nikesh, Lemke-Miltner Caitlin D, Rataan Aseel O, Areecheewakul Sudartip, Bhat Divya S, Lanzel Emily A, Geary Sean M, Simons Andrean L, Weiner George J, Salem Aliasger K
Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA, USA.
Department of Otolaryngology, University of Iowa Hospitals and Clinics, Iowa City, IA, USA.
Cancer Immunol Immunother. 2025 May 3;74(6):189. doi: 10.1007/s00262-025-04023-1.
Leukoplakia, a common type of oral dysplasia, is simply defined as a white patch in the mouth or other mucosal surface. Oral dysplasia is the most common premalignancy in the oral cavity and yet it is insufficiently researched and thus both diagnosing and treating oral dysplasia are still problematic issues. This study focuses on the immune signature of oral dysplasia and explores whether stimulating the immune system with an immune therapy, vidutolimod (± immune checkpoint blockade (ICB)), can prevent the progression of oral dysplasia or even cause regression. Vidutolimod, a virus-like particle encapsulating G10, is believed to activate plasmacytoid dendritic cells (pDCs) through the activation of the Toll-like receptor 9 (TLR9). To investigate this, an established murine model for inducing oral cancer was used to study oral dysplasia development and response to in situ injection of vidutolimod at the premalignant phase. The effect of treatment was analyzed histologically and immunologically. ELISA revealed significantly elevated levels of IFN-γ, IL-12, and TNF-α in the sera of mice after 24 h of one treatment with vidutolimod + ICB as well as increased levels of proliferating T cells and pDCs in draining lymph nodes 72 h after the third and final treatment, thus indicating the immune-boosting effect of this therapy. Vidutolimod + ICB caused a significant decrease in Ki-67 expression by epithelial cells in the lesion area compared to untreated mice, implicating that this treatment regime may prevent lesion progression.
白斑是一种常见的口腔发育异常类型，简单定义为口腔或其他黏膜表面的白色斑块。口腔发育异常是口腔中最常见的癌前病变，但对其研究尚不充分，因此口腔发育异常的诊断和治疗仍然是有问题的。本研究聚焦于口腔发育异常的免疫特征，并探讨用免疫疗法维德托利莫德（±免疫检查点阻断（ICB））刺激免疫系统是否能预防口腔发育异常的进展，甚至使其消退。维德托利莫德是一种包裹G10的病毒样颗粒，据信它通过激活Toll样受体9（TLR9）来激活浆细胞样树突状细胞（pDC）。为了对此进行研究，使用已建立的诱导口腔癌的小鼠模型来研究口腔发育异常的发展以及在癌前阶段原位注射维德托利莫德后的反应。通过组织学和免疫学方法分析治疗效果。酶联免疫吸附测定（ELISA）显示，在单次使用维德托利莫德+ICB治疗24小时后，小鼠血清中干扰素-γ（IFN-γ）、白细胞介素-12（IL-12）和肿瘤坏死因子-α（TNF-α）水平显著升高，并且在第三次也是最后一次治疗72小时后，引流淋巴结中增殖性T细胞和pDC数量增加，这表明该疗法具有免疫增强作用。与未治疗的小鼠相比，维德托利莫德+ICB使病变区域上皮细胞中Ki-67的表达显著降低，这意味着这种治疗方案可能会阻止病变进展。
