固有免疫细胞上Siglec在肿瘤中作用的研究进展与展望

郭朝阳(综述); 胡镜宙(审校)

doi:10.19401/j.cnki.1007-3639.2022.12.012

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固有免疫细胞上Siglec在肿瘤中作用的研究进展与展望

综述 | 更新时间：2025-12-31

- 固有免疫细胞上Siglec在肿瘤中作用的研究进展与展望
- Research progress and prospect of Siglec in innate immune cells in tumor
- 中国癌症杂志 2022年32卷第12期页码：1235-1241
- 作者机构：
  
  1. 潍坊医学院口腔医学院，山东潍坊 261053
  2. 上海交通大学医学院附属第九人民医院口腔颌面-头颈肿瘤科，上海交通大学口腔医学院，国家口腔医学中心，国家口腔疾病临床医学研究中心，上海市口腔医学重点实验室，上海 200011
- 作者简介：
  
  [ "郭朝阳（ORCID: 0000-0002-9416-2670），硕士在读。" ]
  胡镜宙（ORCID: 0000-0003-4402-3370），博士，上海交通大学附属第九人民医院头颈部肿瘤科主任医师。
- 基金信息：
- DOI：10.19401/j.cnki.1007-3639.2022.12.012
  中图分类号： R730.51
- 收稿：2022-08-04，
  
  修回：2022-10-31，
  
  纸质出版：2022-12-30
- 稿件说明：
移动端阅览
郭朝阳(综述), 胡镜宙(审校). 固有免疫细胞上Siglec在肿瘤中作用的研究进展与展望[J]. 中国癌症杂志, 2022,32(12):1235-1241.

Zhaoyang GUO, Jingzhou HU. Research progress and prospect of Siglec in innate immune cells in tumor[J]. China Oncology, 2022, 32(12): 1235-1241.
郭朝阳(综述), 胡镜宙(审校). 固有免疫细胞上Siglec在肿瘤中作用的研究进展与展望[J]. 中国癌症杂志, 2022,32(12):1235-1241. DOI： 10.19401/j.cnki.1007-3639.2022.12.012.

Zhaoyang GUO, Jingzhou HU. Research progress and prospect of Siglec in innate immune cells in tumor[J]. China Oncology, 2022, 32(12): 1235-1241. DOI： 10.19401/j.cnki.1007-3639.2022.12.012.

摘要

免疫治疗给恶性肿瘤患者带来了新的希望。然而，常见的免疫治疗靶点，例如细胞毒性T淋巴细胞相关抗原4（cytotoxic T lymphocyte-associated antigen-4，CTLA-4）、程序性死亡[蛋白

]

配体-1（programmed death ligand-1，PD-L1）在患者中阳性表达率低，只有少部分患者能从免疫治疗中获益，因此寻找新的免疫治疗靶点对于提高免疫治疗的响应率和效果极其重要。近期的研究提示唾液酸结合免疫球蛋白型凝集素（sialic acid-binding immunoglobulin

-type lectin，Siglec）家族在巨噬细胞、自然杀伤（natural killer，NK）细胞和树突状细胞（dendritic cell，DC）等固有免疫细胞上表达丰富，并与肿瘤的发生、发展存在许多联系，有可能成为免疫治疗的下一个新靶点。在巨噬细胞上不同的Siglecs发挥不同的作用，Siglec-1增强巨噬细胞的抗原呈递作用，从而增强CD8

T细胞的杀伤作用；Siglec-7和Siglec-9诱导肿瘤相关巨噬细胞（tumor-associated macrophage，TAM）向免疫抑制性TAM分化从而影响免疫微环境；Siglec-10与CD24相互作用保护肿瘤细胞免受巨噬细胞的攻击，Siglec-15也表现出类似PD-L1的相关作用，这些研究提示其有可能是全新的免疫检查点。NK细胞上高表达Siglec-7和Siglec-9，通过消除NK细胞表面的顺式相互作用，这些Siglec展现出免疫抑制作用。肿瘤表面高表达的唾液酸糖蛋白与NK细胞表面的Siglec相结合从而抑制NK细胞的杀伤作用，通过消除肿瘤表面的唾液酸可以增强NK细胞的杀伤力。有方案设想通过构建高亲合顺式配体来增强NK细胞杀伤力，但发现顺式配体的浓度会对NK细胞的杀伤力造成截然不同的影响，提示唾液酸存在某种动态平衡从而影响免疫反应。DC表面的Siglec-3和Siglec-9会与肿瘤黏蛋白相结合，诱导DC凋亡和减少免疫相关分子的产生进而造成免疫逃逸。在小鼠实验中证实相关Siglec影响DC的抗原呈递和免疫相关因子的表达。本综述总结了近期在固有免疫系统中，Siglec与肿瘤之间的相互作用以及Siglec影响肿瘤发生、发展的相关研究进展，讨论该家族成员作为免疫治疗新靶点的可能。

Abstract

Immunotherapy brings hope to those patients suffering from malignant tumor. However

common immunotherapy targets

such as cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and programmed death ligand-1 (PD-L1)

have low positive expression rate in patients

and only a few patients can benefit from immunotherapy. Therefore

finding new immunotherapy targets is extremely important for improving the response rate and effect of immunotherapy. Recent studies have suggested that sialic acid-binding immunoglobulin-type lectin (Siglec) family members are abundantly expressed in innate immune cells

such as macrophages

natural killer (NK) cells and dendritic cells (DC)

and are shown to be related to the development of tumors. Different Siglecs play different roles in macrophages

and Siglec-1 enhances the antigen presentation of macrophages and thus the killing effect of CD8

T cells. Siglec-7 and Siglec-9 induce the differentiation of tumor-associated macrophages (TAM) to immunosuppressive TAM thus affecting the immune microenvironment. Siglec-10 interacts with CD24 to protect tumor cells from macrophage attack

and Siglec-15 also exhibits PD-L1-like related effects

which suggests that

it may be a novel immune checkpoint. Siglec-7 and Siglec-9 are highly expressed in NK cells

and these Siglecs exhibit immunosuppressive effects by eliminating cis interactions on the surface of NK cells. The highly expressed sialic acid glycoprotein on the tumor surface would bind to Siglecs on the NK cell surface thereby inhibiting the killing effect of NK cells

and the killing effect of NK cells could be enhanced by eliminating sialic acid on the tumor surface. A proposal to enhance NK cell killing by constructing high-affinity cis-ligands revealed that the concentration of cis-ligands had a very different effect on NK cell killing

suggesting that there is a dynamic balance of sialic acid that affects immune reaction. Siglec-3 and Siglec-9 on the surface of DC bind to tumor mucin

inducing DC apoptosis and reducing the production of immune-related molecules

thereby causing immune escape. The related Siglec has been shown to affect the expression of antigen presentation and immune-related factors in DC in mouse experiments. In this review

we summarized the recent studies of Siglecs in the innate immune system on how they interact with tumors and affecting tumor development

and discussed the potential of them as novel targets for immunotherapy.

关键词

Keywords

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