Recent progress in targeting the sialylated glycan-SIGLEC axis in cancer immunotherapy  

作　　者：Yingyan Yu Wenjie Peng 

机构地区：[1]Department of General Surgery of Ruijin Hospital,Shanghai Institute of Digestive Surgery,and Shanghai Key Laboratory for Gastric Neoplasms,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China [2]Shanghai Center for Systems Biomedicine,Shanghai Jiao Tong University,Shanghai 200240,China

出　　处：《Cancer Biology & Medicine》2023年第5期369-384,共16页癌症生物学与医学（英文版）

基　　金：supported by the Shanghai Science and Technology Committee (Grant Nos. 20DZ2201900 to Y.Y. and 23ZR1432500 to W.P.);National Natural Science Foundation of China (Grant Nos. 82072602 to Y.Y.;91853121, 21977066, and 22177069 to W.P.);Innovation Foundation of Translational Medicine of Shanghai Jiao Tong University School of Medicine(Grant No. TM202001 to Y.Y.);Collaborative Innovation Center for Clinical and Translational Science by Chinese Ministry of Education&Shanghai (Grant No. CCTS-2022202 to Y.Y.);Shanghai Pilot Program for Basic Research-Shanghai Jiao Tong University (Grant No. 21TQ1400210 to W.P.);Medical-Engineering Interdisciplinary Research Foundation of Shanghai Jiao Tong University (Grant No. YG2022ZD001 to W.P.)

摘　　要：Malignant tumors are complex structures composed of cancer cells and tumor microenvironmental cells.In this complex structure,cells cross-talk and interact,thus jointly promoting cancer development and metastasis.Recently,immunoregulatory molecule-based cancer immunotherapy has greatly improved treatment efficacy for solid cancers,thus enabling some patients to achieve persistent responses or cure.However,owing to the development of drug-resistance and the low response rate,immunotherapy against the available targets PD-1/PD-L1 or CTLA-4 has limited benefits.Although combination therapies have been proposed to enhance the response rate,severe adverse effects are observed.Thus,alternative immune checkpoints must be identified.The SIGLECs are a family of immunoregulatory receptors(known as glyco-immune checkpoints)discovered in recent years.This review systematically describes the molecular characteristics of the SIGLECs,and discusses recent progress in areas including synthetic ligands,monoclonal antibody inhibitors,and Chimeric antigen receptor T(CAR-T)cells,with a focus on available strategies for blocking the sialylated glycan-SIGLEC axis.Targeting glyco-immune checkpoints can expand the scope of immune checkpoints and provide multiple options for new drug development.

关 键 词：SIGLEC sialylated glycan glyco-immune checkpoint high affinity SIGLEC-ligands anti-SIGLEC antibodies 

分 类 号：R730.51[医药卫生—肿瘤]