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解析逃逸免疫调节因子 Galectin-1、-3 和 -9 及其配体的策略:肿瘤免疫治疗中的新疗法

英文原题:Decoding Strategies to Evade Immunoregulators Galectin-1, -3, and -9 and Their Ligands as Novel Therapeutics in Cancer Immunotherapy.

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Decoding Strategies to Evade Immunoregulators Galectin-1, -3, and -9 and Their Ligands as Novel Therapeutics in Cancer Immunotherapy.

PubMed 2022/12/08(内容时间) Int J Mol Sci Q1 · IF 5.6(JCR 2025)

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中文摘要

半乳糖凝集素是一类β-半乳糖苷结合蛋白,在正常生理过程中发挥多种作用。在癌症中,其表达通常升高,并常与不良预后相关。半乳糖凝集素通过与癌细胞、基质细胞和免疫细胞表面的聚糖结合,推动多条肿瘤进展通路。在哺乳动物的15种半乳糖凝集素中,Gal-1、Gal-3和Gal-9因在肿瘤免疫逃逸中的关键作用而尤受关注。它们不仅促进癌症进展,也会调节抗肿瘤T细胞的存活、分化和功能,从而削弱抗肿瘤免疫及新型免疫疗法的效果。因此,针对其促恶性肿瘤作用的新型抑制策略不断涌现,尤其是通过靶向半乳糖凝集素-聚糖配体相互作用来逆转肿瘤免疫抑制。本文综述干扰Gal-1、Gal-3和Gal-9与配体相互作用、抑制其促肿瘤和免疫调节作用的新策略。这些方法包括中和抗体、合成肽、糖代谢调节剂、竞争性抑制剂、疫苗、基因编辑、细胞外聚糖修饰以及嵌合抗原受体(CAR)T细胞,有望与现有免疫治疗协同,获得高效且持久的应答。

展开英文摘要原文

Galectins are a family of -galactoside-binding proteins that play a variety of roles in normal physiology. In cancer, their expression levels are typically elevated and often associated with poor prognosis. They are known to fuel a variety of cancer progression pathways through their glycan-binding interactions with cancer, stromal, and immune cell surfaces. Of the 15 galectins in mammals, galectin (Gal)-1, -3, and -9 are particularly notable for their critical roles in tumor immune escape. While these galectins play integral roles in promoting cancer progression, they are also instrumental in regulating the survival, differentiation, and function of anti-tumor T cells that compromise anti-tumor immunity and weaken novel immunotherapies.

To this end, there has been a surge in the development of new strategies to inhibit their pro-malignancy characteristics, particularly in reversing tumor immunosuppression through galectin-glycan ligand-targeting methods. This review examines some new approaches to evading Gal-1, -3, and -9-ligand interactions to interfere with their tumor-promoting and immunoregulating activities.

Whether using neutralizing antibodies, synthetic peptides, glyco-metabolic modifiers, competitive inhibitors, vaccines, gene editing, exo-glycan modification, or chimeric antigen receptor (CAR)-T cells, these methods offer new hope of synergizing their inhibitory effects with current immunotherapeutic methods and yielding highly effective, durable responses.

论文信息

作者
Lau LS、Mohammed NBB、Dimitroff CJ
单位
Department of Translational Medicine, Translational Glycobiology Institute at FIU, Herbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, USA.United States
文献类型
综述
期刊
International journal of molecular sciences2022 Dec 8
原文标识
PubMed 36555198 · DOI 10.3390/ijms232415554