Abstract 2015: Mesenchymal stem cell correlates oral leukoplakia malignant transformation through regulate T cell response

Abstract

Abstract Introduction Leukoplakia is one of the most common clinically presented oral potential malignant disorders (OPMD). Detailed understanding of leukoplakia-associated molecular or cellular changes would help us better undertand about the progress of leukoplakia malignant transformation. In this study, we examined the potential involvement of MSC in this very progress, and demonstrated lesion resident MSCs may favour leukoplakia malignant transformation through its strong immunoregulation on T cell. Methods Eighteen six-week-old female Sprague-Dawley rats (180-220g) were given 0.05g/L 4NQO in drinking water for 22 weeks for development of lesions. Lesions classfied by histological HE stainnig. MSCs were obtained from single cell suspesion of lesions, and cultured with splenocyte to study its immunoregulate ability. Results 1. MSC-like cells are enriched in carcinogen induced leukoplakia and cancers. Representative results showing the lesions on tongue of rats. And relative proportion of MSC phenotype marker (CD29+, CD31-, CD45-, CD90+) in oral lesions (OMSC) were counted by flow cytometry. 2. Leukoplakia-derived MSC (L-OMSC), cancer-derived MSC (C-OMSC), and the normal mucosa-derived MSC (N-OMSC) share the similar stemness properties. 3. Cancer lesion have less infiltrating T cells (quantified by IHC and FCM of CD3 ). Cancer-derived MSCs suppress T cell proliferation, but not promote T cell apoptosis and inhibit T cell migration to the lesions. 4. Higher number of lesion derived MSCs associates with higher celluar proliferation in the lesions. Summary Our study demonstrated MSCs could migrate to pre-malignant leukoplakia lesions prior to tumor establishment. Further, MSCs play an important role in leukoplakia malignant transformation induced by chemicals, which via its strong immunomodulatory activities. Citation Format: Yichen Chen, Bailin He, Da Ma, Jingjing Song, Xi Wang, Bin Cheng, Zhi Wang. Mesenchymal stem cell correlates oral leukoplakia malignant transformation through regulate T cell response [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2015. doi:10.1158/1538-7445.AM2017-2015