Xu Haiyan, Yang Ying, Wang PingLi, Lin Shengnan, Zhang Xiaochun, Ni Huiwen, Xu Zhiyong
Department of Biobank, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
Department of Respiratory and Critical Care Medicine, The Fourth Affiliated Hospital of Zhejiang University School of Medicine, Yiwu, China.
Front Immunol. 2025 Jun 3;16:1542526. doi: 10.3389/fimmu.2025.1542526. eCollection 2025.
Adenocarcinoma-to-squamous cell carcinoma transformation (AST) induces drug resistance in patients with lung adenocarcinoma (LUAD), often resulting in unfavorable clinical outcomes. In recent years, it has been found that alterations in the tumor immune microenvironment (TIME) during adenosquamous carcinoma trans-differentiation also influence the efficacy of immunotherapy. Moreover, the aberrant expression and activation of several driver genes for AST lead to abnormal infiltration and function of immune cell by remodeling the cellular inflammatory phenotype. In this review, we will systematically present the changes in the TIME and molecular regulatory mechanisms during adenosquamous carcinoma differentiation, aiming to gain a better understand of the function of immune cells during this process and the potential value of combining immunotherapy to enhance the treatment of non-small cell lung cancer (NSCLC).
腺癌向鳞状细胞癌转化（AST）会导致肺腺癌（LUAD）患者产生耐药性，常常导致不良的临床结局。近年来，已发现腺鳞癌转分化过程中肿瘤免疫微环境（TIME）的改变也会影响免疫治疗的疗效。此外，AST的几个驱动基因的异常表达和激活通过重塑细胞炎症表型导致免疫细胞异常浸润和功能异常。在本综述中，我们将系统地阐述腺鳞癌分化过程中TIME的变化和分子调控机制，旨在更好地了解这一过程中免疫细胞的功能以及联合免疫治疗增强非小细胞肺癌（NSCLC）治疗效果的潜在价值。
