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肿瘤微环境在恶性黑色素瘤类器官肿瘤发生和转移过程中的作用

Role of the tumor microenvironment in malignant melanoma organoids during the development and metastasis of tumors.

作者信息

Zhou Siyu, Lu Jinghan, Liu Shiyang, Shao Jiaqi, Liu Zhanwei, Li Jianjun, Xiao Wan'an

机构信息

Department of Orthopedics, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.

出版信息

Front Cell Dev Biol. 2023 Apr 19;11:1166916. doi: 10.3389/fcell.2023.1166916. eCollection 2023.

Abstract

Malignant melanoma (MM) is the most metastatic and aggressive form of skin cancer, and carries a high risk of death. Immune-checkpoint inhibitor therapy and molecular-targeted therapy can prolong the survival of patients with advanced MM significantly. However, the low response rate and inevitable drug resistance prevent further improvements in efficacy, which is closely related to the tumor microenvironment (TME). The TME refers to the tumor stroma, including fibroblasts, keratinocytes, immune cells, soluble molecules, and extracellular matrix (ECM). The dynamic interaction between the TME and tumor cells is very important for the growth, local invasion, and metastatic spread of tumor cells. A patient-derived organoid (PDO) model involves isolation of tumor tissue from patients with MM and culturing it in a three-dimensional pattern. Compared with traditional cultivation methods, the PDO model preserves the heterogeneity of the tissue structure of MM and demonstrates the interaction between MM cells and the TME. It can reproduce the characteristics of proliferation, migration, and invasion of MM cells, and better simulate the structural function of MM . This review explores the role of each TME component in development of the PDO model. This review will provide a reference for research on the drug screening and targeted treatment using PDOs, particularly for the immunotherapy of MM.

摘要

恶性黑色素瘤(MM)是皮肤癌中最具转移性和侵袭性的类型,且死亡风险很高。免疫检查点抑制剂疗法和分子靶向疗法可显著延长晚期MM患者的生存期。然而,低应答率和不可避免的耐药性阻碍了疗效的进一步提高,而这与肿瘤微环境(TME)密切相关。TME是指肿瘤基质,包括成纤维细胞、角质形成细胞、免疫细胞、可溶性分子和细胞外基质(ECM)。TME与肿瘤细胞之间的动态相互作用对于肿瘤细胞的生长、局部侵袭和转移扩散非常重要。患者来源类器官(PDO)模型涉及从MM患者中分离肿瘤组织并以三维模式进行培养。与传统培养方法相比,PDO模型保留了MM组织结构的异质性,并展示了MM细胞与TME之间的相互作用。它可以重现MM细胞的增殖、迁移和侵袭特征,并更好地模拟MM的结构功能。本综述探讨了每个TME成分在PDO模型发展中的作用。本综述将为使用PDO进行药物筛选和靶向治疗的研究提供参考,特别是对于MM的免疫治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3c1/10154581/f1580d7dade6/fcell-11-1166916-g001.jpg

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