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RS 504393 inhibits M-MDSCs recruiting in immune microenvironment of bladder cancer after gemcitabine treatment
•Monocyte-myeloid derived suppressed cells (M-MDSCs) plays a significant role in immune suppression and contributed to cancer progression, which was increased in bladder cancer (BC) tissue.•This article helps us understand the immune environment of BC deeply.•Gemcitabine treatment promotes the gener...
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Published in: | Molecular immunology 2019-05, Vol.109, p.140-148 |
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Main Authors: | , , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | •Monocyte-myeloid derived suppressed cells (M-MDSCs) plays a significant role in immune suppression and contributed to cancer progression, which was increased in bladder cancer (BC) tissue.•This article helps us understand the immune environment of BC deeply.•Gemcitabine treatment promotes the generation of CCL2 in BC cells, which could recruit M-MDSCs.•This shortage influences the prognosis of BC patients.•RS 504393, a selective CCR2 antagonist, sheds lights on preventing and alleviating side effects of the symptoms occurred on the gemcitabine-treated BC patients, which can improve prognosis of gemcitabine-treated BC patients.
Bladder cancer (BC) is a malignant tumor of urinary epithelium. Gemcitabine is an introduced treatment for BC and also has immunomodulatory function, but the immunoregulation mechanism is not clear. In this study, we found that gemcitabine-treated BC cell recruited more monocyte-myeloid-derived suppressed cells (M-MDSCs), which played a significant role in immune suppression and contributed to cancer progression. We found that this phenomenon was induced by Chemokine (C-C motif) ligand 2 (CCL2), an M-MDSCs recruitment related monomeric polypeptide. Gemcitabine treatment promotes the generation of CCL2 and CCL2 could attach to C-C chemokine receptor type 2 (CCR2) to recruit M-MDSCs. We used RS 504393, a selective CCR2 antagonist, to inhibit the recruitment of M-MDSCs. RS 504393 improved the prognosis by blocking chemotaxis of M-MDSCs, and this finding sheds lights on how to prevent and alleviate the side effects occurred on the gemcitabine-treated BC patients. |
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ISSN: | 0161-5890 1872-9142 |
DOI: | 10.1016/j.molimm.2019.02.014 |