清华大学刘鹏研究组近日取得一项新成果。经过不懈努力，他们研制了探讨肺癌全身抗肿瘤免疫的类器官共培养模型。2025年6月12日出版的《细胞—干细胞》杂志发表了这项成果。

该课题组建立了肺癌类器官（LCOs）和配对外周血单个核细胞（PBMCs）的凝胶-液界面（GLI）共培养模型，该模型增强了免疫细胞与肿瘤类器官之间的相互作用，优化了体内全身抗肿瘤免疫的模拟。通过构建肺癌患者队列，该课题组人员证明GLI模型在αPD1治疗下的反应准确反映了相应患者的免疫治疗结果。

此外，该团队通过功能多组学分析，剖析了GLI模型中由PBMC衍生的T细胞介导的各种肿瘤免疫过程，以及具有效应记忆样表型的循环肿瘤反应性T细胞（GNLY⁺CD44⁺CD9⁺）的特征，作为免疫治疗疗效的潜在指标。他们的研究结果表明，GLI共培养模型可以以开发精确免疫疗法的诊断策略为主题，并了解其潜在机制。

据悉，解读肿瘤微观和全身免疫宏观环境之间的相互作用对于制定更有效的癌症诊断和治疗策略至关重要。

附：英文原文

Title: An organoid co-culture model for probing systemic anti-tumor immunity in lung cancer

Author: Kaiyi Li, Chang Liu, Xizhao Sui, Chao Li, Ting Zhang, Tian Zhao, Dong Zhang, Hainan Wu, Yuhan Liu, Shuai Wang, Yingshun Yang, Baobao Lin, Wenyan Wang, Fan Yang, Xiaofang Chen, Peng Liu

Issue&Volume: 2025-06-12

Abstract: Deciphering interactions between tumor micro- and systemic immune macroenvironments is essential for developing more effective cancer diagnosis and therapeutic strategies. Here, we established a gel-liquid interface (GLI) co-culture model of lung cancer organoids (LCOs) and paired peripheral-blood mononuclear cells (PBMCs), featuring enhanced interactions between immune cells and tumor organoids for optimized simulation of in vivo systemic anti-tumor immunity. By constructing a cohort of lung cancer patients, we demonstrated that the responses of GLI models under αPD1 treatment reflected the immunotherapy outcomes of the corresponding patients precisely. Furthermore, we dissected the various tumor immune processes mediated by PBMC-derived T cells within GLI models through functional multi-omics analyses, along with the characterization of circulating tumor-reactive T cells (GNLY+CD44+CD9+) with effector memory-like phenotypes as a potential indicator of immunotherapy efficacy. Our findings indicate that the GLI co-culture model can be used to develop diagnostic strategies for precision immunotherapies, as well as understanding the underlying mechanisms.

DOI: 10.1016/j.stem.2025.05.011

Source: https://www.cell.com/cell-stem-cell/abstract/S1934-5909(25)00191-2