Yao Ningning, Jing Na, Lin Jianzhong, Niu Wenxia, Yan Wenxing, Yuan Hongqin, Xiong Zeyi, Hou Qing, Qiao Xiaxi, Liu Quanming, Cao Jianzhong, Li Ning
Department of Radiotherapy, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, No.3, Zhigong New Street, Xinghualing District, Taiyuan, 030013, China.
Department of Urology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210011, China.
Invest New Drugs. 2025 Apr;43(2):394-404. doi: 10.1007/s10637-025-01523-w. Epub 2025 Apr 15.
Cancer immunotherapy has revolutionized tumor treatment. However, robust and effective testing platforms remain lacking, especially for the selection of the optimized therapy at the patient-specific level. Unlike conventional treatment evaluations, testing platforms for cancer immunotherapy must incorporate not only tumor cells but also the tumor microenvironment (TME), including immune components. Recently, emergence of patient-derived tumor organoids (PDTOs), an in vitro preclinical model, has provided a novel approach for studying tumor evolution and assessing treatment responses, and shows great potential when coculturing with immune cells to study the mechanisms of immunotherapy efficacy and resistance. However, traditional organoid technology is limited in capturing the full impact of the TME on tumor behaviors due to the absence of stromal components. To circumvent these restrictions, complex organoid cocultures with immune cells, cancer-associated fibroblasts and vasculatures are developed. In this review, we summarized recent advances in PDTO culture techniques for modeling the TME and explored the application of complex tumor organoids in cancer immunotherapy.
癌症免疫疗法彻底改变了肿瘤治疗方式。然而,目前仍缺乏强大且有效的测试平台,尤其是在患者个体水平上选择优化治疗方案方面。与传统治疗评估不同,癌症免疫疗法的测试平台不仅必须纳入肿瘤细胞,还必须纳入肿瘤微环境(TME),包括免疫成分。最近,患者来源的肿瘤类器官(PDTOs)这一临床前体外模型的出现,为研究肿瘤演变和评估治疗反应提供了一种新方法,并且在与免疫细胞共培养以研究免疫治疗疗效和耐药机制时显示出巨大潜力。然而,由于缺乏基质成分,传统类器官技术在捕捉TME对肿瘤行为的全面影响方面存在局限性。为了规避这些限制,人们开发了与免疫细胞、癌症相关成纤维细胞和脉管系统的复杂类器官共培养体系。在这篇综述中,我们总结了用于模拟TME的PDTO培养技术的最新进展,并探讨了复杂肿瘤类器官在癌症免疫疗法中的应用。