Tumor-derived microparticles promote the progression of triple-negative breast cancer via PD-L1-associated immune suppression


Posted: 2021-10-03 19:00:00
Cancer Lett . 2021 Sep 30;S0304-3835(21)00500-0. doi: 10.1016/j.canlet.2021.09.039. Online ahead of print. Affiliations Expand Affiliations 1 Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17, Panjiayuannanli, Chaoyang District, 100021, Beijing, China. 2 Department of Urology, Institute of Urology, National Clinical Research Center for Geriatrics and Center of Biomedical Big Data, West China Hospital of Sichuan University, Chengdu, 610041, China. 3 Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17, Panjiayuannanli, Chaoyang District, 100021, Beijing, China. Electronic address: xubinghe@medmail.com.cn. 4 State Key Laboratory of Biotherapy and Cancer Center, Sichuan University, Chengdu, 610041, China. Electronic address: jinxunpumc@126.com. Item in Clipboard Cong Li et al. Cancer Lett. 2021. Show details Display options Display options Format Cancer Lett . 2021 Sep 30;S0304-3835(21)00500-0. doi: 10.1016/j.canlet.2021.09.039. Online ahead of print. Affiliations 1 Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17, Panjiayuannanli, Chaoyang District, 100021, Beijing, China. 2 Department of Urology, Institute of Urology, National Clinical Research Center for Geriatrics and Center of Biomedical Big Data, West China Hospital of Sichuan University, Chengdu, 610041, China. 3 Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17, Panjiayuannanli, Chaoyang District, 100021, Beijing, China. Electronic address: xubinghe@medmail.com.cn. 4 State Key Laboratory of Biotherapy and Cancer Center, Sichuan University, Chengdu, 610041, China. Electronic address: jinxunpumc@126.com. Item in Clipboard CiteDisplay options Display options Format Abstract Membrane vesicles, including exosomes and microparticles (MPs), serve to package and transfer the cellular cargo during inter/extracellular communication, which is of great interest in cancer development, especially in the dissemination of signal transduction-associated traits from donor cells to recipient cells. Although increasing evidence suggests that microparticles (MPs) contribute to the development of cancer, their unique characteristics remain to be exploited. Here, we examined the secretion of MPs in tumor tissues from triple-negative breast cancer (TNBC) patients and found that the tumor cells could release MPs loaded with immune checkpoint molecular programmed cell death ligand 1 (PD-L1), especially in patients treated with traditional clinical interventions, such as chemotherapy and radiotherapy. These PD-L1-loading MPs contribute to the suppressive immune microenvironment, eventually resulting in the tumor progression in TNBC. Mechanically, we proved that PD-L1-loading MPs could suppress the activation and function of functional cluster of differentiation (CD)-8+ T cells. Meanwhile, the PD-L1-loading MPs could mediate the differentiation of macrophages toward the immune-suppressive M2 phenotype via the activation of the TANK-binding kinase 1 (TBK1)/signal transducer and activator of transcription 6 (STAT6) signal and suppression of the serine-threonine kinase (AKT)/mammalian target of rapamycin (mTOR) signal. Given the increasing MP production induced by traditional clinical interventions, we further combined chemotherapy with the PD-L1 inhibitor atezolizumab (ATZ) to efficiently abrogate the immunosuppression caused by the PD-L1-loading MPs. Therefore, our study unveils the mechanism by which tumor cells systemically evade immune surveillance by releasing the PD-L1-loading MPs, and provides new insights into clinical TNBC immunotherapy. Keywords: Immune microenvironment; Macrophage polarization; Membrane vesicles; PD-L1. Copyright © 2021. Published by Elsevier B.V. [x] Cite Copy Format: Send To [x]

参考サイト PubMed: exsome



バイオクイックニュース日本語版:エクソソーム特集

バイオクイックニュース日本語版
3月 07, 2019 バイオアソシエイツ

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ゲスト 525人 と メンバー 2人 がオンラインです