肿瘤微环境免疫细胞调节肿瘤细胞耐药性的研究进展

doi:10.3969/j.issn.1674-8115.2024.07.004

上海交通大学学报（医学版） ›› 2024, Vol. 44 ›› Issue (7): 830-838.doi: 10.3969/j.issn.1674-8115.2024.07.004

• 转化医学研究前沿进展专题 • 上一篇

肿瘤微环境免疫细胞调节肿瘤细胞耐药性的研究进展

张烨晟¹(), 杨易静¹, 黄依雯², 施珑玙³, 王曼媛⁴, 陈思思⁵()

^1.上海交通大学医学院附属上海儿童医学中心儿科转化医学研究所，上海 200127
^2.上海交通大学医学院附属胸科医院胸部肿瘤研究所，上海 200030
^3.上海交通大学医学院附属仁济医院干细胞研究中心，上海 200127
^4.上海交通大学医学院医学技术学院，上海 200025
^5.上海交通大学医学院附属第一人民医院疑难疾病精准研究中心，上海 201600

收稿日期:2024-01-30 接受日期:2024-04-28 出版日期:2024-07-28 发布日期:2024-07-28
通讯作者: 陈思思 E-mail:yesheng_zhang@163.com;sisichen@shsmu.edu.cn
作者简介:张烨晟（2001—），男，博士生；电子信箱：yesheng_zhang@163.com。
基金资助:
上海市浦江人才计划(23PJ1410400)

Research progress in immune cells regulating drug resistance of tumor cells in tumor microenvironment

ZHANG Yesheng¹(), YANG Yijing¹, HUANG Yiwen², SHI Longyu³, WANG Manyuan⁴, CHEN Sisi⁵()

^1.Pediatric Translational Medicine Institute, Shanghai Children′s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
^2.Shanghai Institute of Thoracic Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
^3.Clinical Stem Cell Research Center, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
^4.College of Health Science and Technology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
^5.Precision Research Center for Refractory Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201600, China

Received:2024-01-30 Accepted:2024-04-28 Online:2024-07-28 Published:2024-07-28
Contact: CHEN Sisi E-mail:yesheng_zhang@163.com;sisichen@shsmu.edu.cn
Supported by:
Shanghai Pujiang Program(23PJ1410400)

摘要/Abstract

摘要：

肿瘤微环境（tumor microenvironment，TME）是肿瘤细胞生存的复杂细胞环境，内含多种类型的细胞和围绕肿瘤细胞的细胞外成分。免疫细胞是TME的关键组成部分，包括肿瘤相关巨噬细胞（tumor-associated macrophages，TAMs）、髓系抑制性细胞（myeloid-derived suppressor cells，MDSCs）、淋巴细胞、调节性T细胞（regulatory T cells，Tregs）、自然杀伤细胞（natural killer cells，NK cells）及树突状细胞（dendritic cells，DCs）等。值得关注的是，目前肿瘤耐药是化学治疗（化疗）、放射治疗（放疗）、靶向治疗及免疫治疗等肿瘤治疗方法疗效受限并导致治疗失败的主要原因。研究发现，肿瘤细胞耐药性的产生是肿瘤细胞与TME相互作用的结果。因此，如何克服TME所致肿瘤耐药被认为是肿瘤治疗的一大难点。近年来，随着对TME中免疫细胞研究的深入，免疫细胞调节肿瘤细胞耐药性的具体机制研究取得重大进展，而靶向相应免疫细胞、信号通路或细胞因子的治疗策略被证实能够有效减少肿瘤耐药并改善肿瘤治疗效果。该文就TME中TAMs、MDSCs、Tregs和NK细胞等在肿瘤耐药中发挥的作用及克服肿瘤耐药的靶向策略的研究进展进行综述，并讨论肿瘤相关中性粒细胞（tumor-associated neutrophils，TANs）和免疫抑制性调节性B细胞（B regulatory cells，Bregs）与肿瘤耐药之间的关系，以期为克服肿瘤耐药和提高抗肿瘤治疗效果提供方向和参考。

关键词: 肿瘤微环境, 耐药, 肿瘤相关巨噬细胞, 髓系抑制性细胞, 调节性T细胞, 自然杀伤细胞

Abstract:

Tumor microenvironment (TME) is a complex cellular environment where tumor cells reside, along with various types of cells and extracellular components surrounding the tumor cells. Immune cells are key components of TME, including tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), lymphocytes, regulatory T cells (Tregs), natural killer cells (NK cells), dendritic cells (DCs), and many others. It is worth noting that drug resistance is currently a major factor limiting the efficacy of cancer treatment methods such as chemotherapy, radiotherapy, targeted therapy, and immunotherapy, and a leading cause of treatment failure. Research has found that the development of drug resistance in tumor cells is the result of interactions between tumor cells and TME. Consequently, overcoming drug resistance in tumors caused by TME is considered a significant challenge in cancer treatment. In recent years, with in-depth research into immune cells within TME, significant progress has been made in understanding the specific mechanisms by which immune cells regulate drug resistance in tumor cells. Furthermore, therapeutic strategies that target these immune cells, signaling pathways, or cytokines have been shown to effectively combat tumor drug resistance and enhance the therapeutic outcomes of cancer treatment. This article reviews the research advancements regarding the roles of TAMs, MDSCs, Tregs, and NK cells in tumor drug resistance within TME and discusses the development of targeting strategies to overcome this resistance. Additionally, we explore the relationship of tumor-associated neutrophils (TANs) and B regulatory cells (Bregs) with tumor drug resistance. It is hoped that this review will offer insights and serve as reference for reducing tumor drug resistance and improving the efficacy of anti-tumor therapies.

Key words: tumor microenvironment (TME), drug resistance, tumor-associated macrophage (TAM), myeloid-derived suppressor cell (MDSC), regulatory T cell (Treg), natural killer cell (NK cell)

中图分类号:

R730.3

张烨晟, 杨易静, 黄依雯, 施珑玙, 王曼媛, 陈思思. 肿瘤微环境免疫细胞调节肿瘤细胞耐药性的研究进展[J]. 上海交通大学学报（医学版）, 2024, 44(7): 830-838.

ZHANG Yesheng, YANG Yijing, HUANG Yiwen, SHI Longyu, WANG Manyuan, CHEN Sisi. Research progress in immune cells regulating drug resistance of tumor cells in tumor microenvironment[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2024, 44(7): 830-838.

图/表 1

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肿瘤微环境免疫细胞调节肿瘤细胞耐药性的研究进展

Research progress in immune cells regulating drug resistance of tumor cells in tumor microenvironment

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