慢性炎症对食管腺癌(EAC)和食管鳞状细胞癌(ESCC)的发展至关重要，尽管后者与反流性食管炎无关。L2-IL-1β转基因小鼠在口腔、食管和缘胃鳞状上皮中表达人类白细胞介素(IL)-1β，特征为慢性炎症和鳞状柱细胞交界处巴雷特食管样化生变、异型增生和腺癌的逐步发展。然而，IL-1β介导的口腔和食管鳞状上皮的功能后果仍不明确。我们首次报道了L2-IL-1β小鼠不仅出现了前述的巴雷特食管样化生变，还发展出了鳞状上皮异型增生并进展为食管和舌头的鳞状细胞癌(SCC)。L2-IL-1β小鼠显示了鳞状增生向SCC的年龄相关进展，12-15个月大时，食管侵袭性SCC的发病率约为40%(n=49)，舌头侵袭性SCC的发病率约为23.5%(n=17)。有趣的是，L2-IL-1β小鼠中SCC的发展和进展在无菌和特定病原体自由条件下相似。免疫组织化学显示，在L2-IL-1β小鼠的异型增生鳞状上皮中，主要表现为T细胞为主导的炎症特征，Ki67、Sox2和DNA双链断裂标志物γ-H2AX的表达升高。在L2-IL-1β小鼠的食管和舌头组织中，促炎细胞因子、免疫调节因子、炎症细胞的趋化因子(T细胞、中性粒细胞、嗜酸粒细胞和巨噬细胞)以及氧化损伤标志物iNOS均显著增加。我们最近的发现扩展了IL-1β小鼠模型的翻译用途，有助于进一步揭示炎症驱动的BE、EAC以及ESCC和口腔SCC的关键途径。© 2023.Springer Nature Limited.

Chronic inflammation is integral to the development of esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC), although the latter has not been associated with reflux esophagitis. The L2-IL-1β transgenic mice, expressing human interleukin (IL)-1β in the oral, esophageal and forestomach squamous epithelia feature chronic inflammation and a stepwise development of Barrett's esophagus-like metaplasia, dysplasia and adenocarcinoma at the squamo-columnar junction. However, the functional consequences of IL-1β-mediated chronic inflammation in the oral and esophageal squamous epithelia remain elusive. We report for the first time that in addition to the previously described Barrett's esophagus-like metaplasia, the L2-IL-1β mice also develop squamous epithelial dysplasia with progression to squamous cell carcinoma (SCC) in the esophagus and the tongue. L2-IL-1β showed age-dependent progression of squamous dysplasia to SCC with approximately 40% (n = 49) and 23.5% (n = 17) incidence rates for esophageal and tongue invasive SCC respectively, by 12-15 months of age. Interestingly, SCC development and progression in L2-IL-1β was similar in both Germ Free (GF) and Specific Pathogen Free (SPF) conditions. Immunohistochemistry revealed a T cell predominant inflammatory profile with enhanced expression of Ki67, Sox2 and the DNA double-strand break marker, γ-H2AX, in the dysplastic squamous epithelia of L2-IL-1β mice. Pro-inflammatory cytokines, immunomodulatory players, chemoattractants for inflammatory cells (T cells, neutrophils, eosinophils, and macrophages) and oxidative damage marker, iNOS, were significantly increased in the esophageal and tongue tissues of L2-IL-1β mice. Our recent findings have expanded the translational utility of the IL-1β mouse model to aid in further characterization of the key pathways of inflammation driven BE and EAC as well as ESCC and Oral SCC.© 2023. Springer Nature Limited.