Patient-derived tumor-like cell clusters for personalized chemo- and immunotherapies in non-small cell lung cancer

• DOI: 10.1016/j.stem.2024.03.008
• Publication Date: 2024-04-08T14:34:33Z
• Authors: Shenyi Yin; Ying Yu; Nan Wu; Minglei Zhuo; Yanmin Wang; Yanjie Niu; Yiqian Ni; Fang Hu; Cuiming Ding; Hongsheng Liu; Xinghua Cheng; Jin Peng; Juan Li; Yang He; Jiaxin Li; Junyi Wang; Hanshuo Zhang; Xiaoyu Zhai; Bing Liu; Yaqi Wang; Shi Yan; Mailin Chen; Wenqing Li; Jincui Peng; Fei Peng; Ruibin Xi; Buqing Ye; Liyan Jiang; Jianzhong Jeff Xi
• Keywords: Male; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Humans; Animals; Female; Immunotherapy; Precision Medicine

Many patient-derived tumor models have emerged recently. However, their potential to guide personalized drug selection remains unclear. Here, we report patient-derived tumor-like cell clusters (PTCs) for non-small cell lung cancer (NSCLC), capable of conducting 100-5,000 drug tests within 10 days. We have established 283 PTC models with an 81% success rate. PTCs contain primary tumor epithelium self-assembled with endogenous stromal and immune cells and show a high degree of similarity to the original tumors in phenotypic and genotypic features. Utilizing standardized culture and drug-response assessment protocols, PTC drug-testing assays reveal 89% overall consistency in prospectively predicting clinical outcomes, with 98.1% accuracy distinguishing complete/partial response from progressive disease. Notably, PTCs enable accurate prediction of clinical outcomes for patients undergoing anti-PD1 therapy by combining cell viability and IFN-γ value assessments. These findings suggest that PTCs could serve as a valuable preclinical model for personalized medicine and basic research in NSCLC.