消化道肿瘤免疫抑制性微环境研究进展

李宇婷; 谭香玉; 黄柳娜; 马理想; 付利

doi:10.12182/20220160501

消化道肿瘤免疫抑制性微环境研究进展

doi:

杭州省区域性免役与皮肤疾病要点实验操作室郑州本科大家国际联盟肉瘤中心局郑州本科大家临床医美部基本条件临床医美院药理学系（郑州 518060）

基金项目: 国家自然科学基金面上项目（No. 81772957）、广东省组织器官区域免疫与疾病重点实验室项目（No. 2019B030301009）和深圳市工信局双链项目（No. 20180309100135860）资助

详细信息

通讯作者:
E-mail：gracelfu@szu.edu.cn

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出版历程
- 收稿日期: 2022-09-20
- 修回日期: 2022-12-21
- 网络出版日期: 2023-01-24
- 刊出日期: 2023-01-24

Research Progress in Immunosuppressive Tumor Microenvironment of Gastrointestinal Cancer

Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, International Cancer Center of Shenzhen University, and Department of Pharmacology, School of Basic Medical Sciences, Health Science Center, Shenzhen University, Shenzhen 518060, China

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Corresponding author: E-mail: gracelfu@szu.edu.cn

摘要

摘要: 消化道肿瘤（gastrointestinal cancer, GI）是我国常见高发的恶性肿瘤，随着其发病率的日益升高和愈发年轻化的趋势，新的治疗技术也在不断发展和创新，其中免疫疗法正在引领消化道肿瘤治疗新时代。然而，免疫抑制性肿瘤微环境（tumor microenvironment, TME）的复杂性和多样性给消化道实体瘤的免疫治疗增添了重重阻碍。本综述以消化道实体肿瘤为切入点，回顾了影响其免疫抑制性微环境形成的主要因素，概述了靶向免疫抑制微环境治疗的策略，分析了各类免疫联合疗法的协同机制，总结了消化道恶性肿瘤患者免疫治疗的最新进展和未来方向，旨在为消化道实体瘤的免疫治疗提供新思路。
- 消化道肿瘤 /
- 免疫抑制性肿瘤微环境 /
- 免疫疗法 /
- 肿瘤治疗
Abstract: Gastrointestinal (GI) cancer, a common malignant tumor with a high incidence in China, is showing a trend of rising incidence and is afflicting increasingly younger patients. Meanwhile, there have been constant development and innovations in new therapeutic technologies, among which, immunotherapy is now leading in a new era in the treatment of GI cancer. However, the complexity and diversity of immunosuppressive tumor microenvironment (TME) bring many obstacles to the immunotherapy of solid tumors in the GI tract. In this paper, focusing on solid tumors in the GI tract, we reviewed the main factors affecting the formation of immunosuppressive TME, and summarized strategies for targeted immunosuppressive TME-based therapies. Moreover, we analyzed the synergistic mechanism of various combination immunotherapies and reported on the latest progress in and future direction of immunotherapy for GI cancer, intending to provide new perspectives for treating solid tumors in the GI tract with immumotherapy.
- Gastrointestinal cancer /
- 🙈 Immunosuppressive tumor microenvironment /
- Immunotherapy /
- Anti-tumor therapy

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图 1 消化道肿瘤免疫抑制性微环境的组成模式图

Figure 1. 🥂 A schematic illustration of the immunosuppressive tumor microenvironment in gastrointestinal cancer
MDSCs: Myeloid-derived suppressor cells; VEGF: Vascular endothelial growth factor; CTL: Cytotoxic T lymphocytes; Th1: Effector T helper 1 cells; Th17: Effector T helper 17 cells; Tregs: Regulatory T cells; DCs: Dendritic cells; TAMs: Tumor-associated macrophages; TANs: Tumour-associated neutrophils; CSCs: Cancer stem cells; CTLA4: Cytotoxic T lymphocyte antigen 4; TIM3: T cell immunoglobulin and mucin domain-containin protein 3; PD1: Programmed cell death protein 1; IDO: Indoleamine 2,3-dioxygenase; IL: Interleukin; ROS: Reactive oxygen species; TGF-β: Transforming growth factor-β; CXCL12: C-X-C motif chemokine ligand 12; CXCR4: C-X-C motif chemokine receptor 4.

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图 2 消化道肿瘤免疫抑制性微环境的腺苷通路图

Figure 2. ♎ Adenosinergic pathway in the immunosuppressive tumor microenvironment in gastrointestinal cancer
FOXP3: Forkhead box P3; LAG3: Lymphocyte activation gene 3; IFN-γ: Interferon-γ; TNF: Tumour necrosis factor; TCR: T cell receptor; ATP: Adenosine triphosphate; PKA: Protein kinase A; cAMP: Cyclic AMP; HIF1A: Hypoxia-inducible factor 1A; NF-κB: Nuclear factor-κB; MHC Ⅱ: Major histocompatibility complex class Ⅱ; TLR4: Toll-like receptor 4.

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图 3 靶向消化道肿瘤免疫抑制微环境的治疗策略模式图

Figure 3. ๊ Immunosuppressive TME-based therapeutical strategies in gastrointestinal cancer
HDAC: Histone deacetylase; TRAILR2: TNF-related apoptosis-inducing ligand receptor 2; TLR9: Toll like receptor 9.

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