The link between intracellular calcium signaling and exosomal PD-L1 in cancer progression and immunotherapy

作     者：Md Rakibul Alam Md Mizanur Rahman Zhiguo Li Md Rakibul Alam;Md Mizanur Rahman;Zhiguo Li

作者机构：Department of Toxicology and Cancer BiologyCollege of MedicineUniversity of KentuckyLexingtonKY 40506USA Department of Medicine(Nephrology)Faculty of Medicine and DentistryUniversity of AlbertaEdmontonAlberta T6E2H7Canada 

出 版 物：《Genes & Diseases》 (基因与疾病（英文）)

年 卷 期：2024年第11卷第1期

页      面：321-334页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by the National Institutes of Health(No.R01 CA266579 to Zhiguo Li) partially supported by the UK CARES Career Development Program(No.P30 ES026529) theAmerican CancerSociety(No.IRG19-140-31) 

主　　题：Calcium signaling CD8^(+)T cells Exosomal PD-L1 Exosomes biogenesis Immunosuppression Immunotherapy 

摘      要：Exosomes are small membrane vesicles containing microRNA,RNA,DNA fragments,and proteins that are transferred from donor cells to recipient *** cells release exo-somes to reprogram the factors associated with the tumor microenvironment(TME)causing tu-mor metastasis and immune *** evidence revealed that cancer cell-derived exosomes carry immune inhibitory molecule program death ligand 1(PD-L1)that binds with re-ceptor program death protein 1(PD-1)and promote tumor progression by escaping immune ***,some FDA-approved monoclonal antibodies are clinicallyused for cancer treatment by blocking PD-1/PD-L1 *** notable treatment outcomes,some pa-tients show poor drug *** PD-L1 plays a vital role in lowering the treatment response,showing resistance to PD-1/PD-L1 blockage therapy through recapitulating the ef-fect of cell surface *** enhance therapeutic response,inhibition of exosomal PD-L1 is *** signaling is the central regulator of tumorigenesis and can regulate exosome biogenesis and secretion by modulating Rab GTPase family and membrane fusion ***-mune checkpoints are also connected with calcium signaling and calcium channel blockers like amlodipine,nifedipine,lercanidipine,diltiazem,and verapamil were also reported to suppress cellular PD-L1 ***,to enhance the PD-1/PD-L1 blockage therapy response,the reduction of exosomal PD-L1 secretion from cancer cells is in our therapeutic *** this review,we proposed a therapeutic strategy by targeting calcium signaling to inhibit the expression of PD-L1-containing exosome levels that could reduce the anti-PD-1/PD-L1 therapy resistance and increase the patient s drug response rate.