Decoding Strategies to Evade Immunoregulators Galectin-1, -3, and -9 and Their Ligands as Novel Therapeutics in Cancer Immunotherapy.
Decoding Strategies to Evade Immunoregulators Galectin-1, -3, and -9 and Their Ligands as Novel Therapeutics in Cancer Immunotherapy.
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DOI：
10.3390/ijms232415554
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发表时间：
2022-12-08
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
半乳糖凝集素是一个ß-半乳糖苷结合蛋白家族，在正常生理中发挥多种作用。在癌症中，它们的表达水平通常升高，通常与预后不良有关。众所周知，它们通过与癌症、基质和免疫细胞表面的聚糖结合相互作用，促进了多种癌症进展途径。在哺乳动物的15种半乳糖凝集素中，半乳糖凝集素(Gal)-1、-3和-9在肿瘤免疫逃逸中发挥着重要作用。虽然这些凝集素在促进癌症进展中发挥着不可或缺的作用，但它们也有助于调节抗肿瘤T细胞的生存、分化和功能，从而损害抗肿瘤免疫并削弱新的免疫疗法。为此，抑制其促恶性特性的新策略的发展激增，特别是通过半乳糖凝集素-聚糖配体靶向方法逆转肿瘤免疫抑制。本文综述了逃避Gal-1、-3和-9配体相互作用以干扰其促肿瘤和免疫调节活性的一些新方法。无论是使用中和抗体、合成肽、糖代谢修饰剂、竞争性抑制剂、疫苗、基因编辑、外聚糖修饰或嵌合抗原受体(CAR)-T细胞，这些方法都为它们与当前免疫治疗方法协同抑制作用并产生高效、持久的反应提供了新的希望。
Galectins are a family of ß-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.
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DOI：
10.1182/asheducation-2012.1.143
发表时间：
2012
期刊：
Hematology. American Society of Hematology. Education Program
影响因子：
--
作者：
Brentjens RJ;Curran KJ
通讯作者：
Curran KJ
影响因子：
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影响因子：
7.2
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Bendtsen SK;Perez-Penco M;Hübbe ML;Martinenaite E;Orebo Holmström M;Weis-Banke SE;Grønne Dahlager Jørgensen N;Jørgensen MA;Munir Ahmad S;Jensen KM;Friese C;Lundsager MT;Johansen AZ;Carretta M;Ødum N;Met Ö;Svane IM;Madsen DH;Andersen MH
通讯作者：
Andersen MH
DOI：
10.1016/j.jbc.2020.100212
发表时间：
2021-01
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
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通讯作者：
Kimber MS
影响因子：
11.2
作者：
Bull, Christian;Boltje, Thomas J.;Adema, Gosse J.
通讯作者：
Adema, Gosse J.