Circulating tumor cells shielded with extracellular vesicle-derived CD45 evade T cell attack to enable metastasis  

作　　者：Chuan Yang Xueping Wang Kenneth K.W.To Caimei Cui Min Luo Shaocong Wu Lamei Huang Kai Fu Can Pan Zeyu Liu Teng Fan Caibo Yang Fang Wang Liwu Fu 

机构地区：[1]State Key Laboratory of Oncology in South China,Guangdong Provincial Clinical Research Center for Cancer,Sun Yat-sen University Cancer Center,Guangzhou 510060,P.R.China [2]School of Pharmacy,Faculty of Medicine,The Chinese University of Hong Kong,Hong Kong,China [3]LABVIV Technology(Shenzhen)Co.,Ltd,Shenzhen 518057,China

出　　处：《Signal Transduction and Targeted Therapy》2024年第5期2114-2131,共18页信号转导与靶向治疗（英文）

基　　金：supported by the National Natural Science Foundation of China(No:U21A20421,82073882,82203649);the Key Project of Science Technology Program of Guangzhou(No:2023B03J0029);National Key R&D Program of China(No:2022YFE0209700).

摘　　要：Circulating tumor cells(CTCs)are precursors of distant metastasis in a subset of cancer patients.A better understanding of CTCs heterogeneity and how these CTCs survive during hematogenous dissemination could lay the foundation for therapeutic prevention of cancer metastasis.It remains elusive how CTCs evade immune surveillance and elimination by immune cells.In this study,we unequivocally identified a subpopulation of CTCs shielded with extracellular vesicle(EVs)-derived CD45(termed as CD45^(+)CTCs)that resisted T cell attack.A higher percentage of CD45^(+)CTCs was found to be closely correlated with higher incidence of metastasis and worse prognosis in cancer patients.Moreover,CD45^(+)tumor cells orchestrated an immunosuppressive milieu and CD45^(+)CTCs exhibited remarkably stronger metastatic potential than CD45−CTCs in vivo.Mechanistically,CD45 expressing on tumor surfaces was shown to form intercellular CD45-CD45 homophilic interactions with CD45 on T cells,thereby preventing CD45 exclusion from TCR-pMHC synapse and leading to diminished TCR signaling transduction and suppressed immune response.Together,these results pointed to an underappreciated capability of EVs-derived CD45-dressed CTCs in immune evasion and metastasis,providing a rationale for targeting EVs-derived CD45 internalization by CTCs to prevent cancer metastasis.

关 键 词：CD45 METASTASIS PREVENTION 

分 类 号：R730.3[医药卫生—肿瘤]