التفاصيل البيبلوغرافية
| العنوان: |
Accumulation of blood-circulating PD-L1-expressing M-MDSCs and monocytes/macrophages in pretreatment ovarian cancer patients is associated with soluble PD-L1 |
| المؤلفون: |
Karolina Okła, Alicja Rajtak, Arkadiusz Czerwonka, Marcin Bobiński, Anna Wawruszak, Rafał Tarkowski, Wiesława Bednarek, Justyna Szumiło, Jan Kotarski |
| المصدر: |
Journal of Translational Medicine, Vol 18, Iss 1, Pp 1-17 (2020) |
| بيانات النشر: |
BMC, 2020. |
| سنة النشر: |
2020 |
| المجموعة: |
LCC:Medicine |
| مصطلحات موضوعية: |
Ovarian cancer, M-MDSC, Monocytes/macrophages, PD-L1, sPD-L1, TMEs, Medicine |
| الوصف: |
Abstract Background Previous studies have shown clinical relevance of programmed death-ligand 1 (PD-L1) and soluble PD-L1 (sPD-L1) in human cancers. However, still contradictory results exist. Our aim was evaluation of PD-L1-expressing monocytic myeloid-derived suppressor cells (M-MDSCs), monocytes/macrophages (MO/MA), tumour cells (TC) and immune/inflammatory cells (IC) as well as investigation of the sPD-L1 in ovarian cancer (OC) patients. Methods The group of 74 pretreatment women were enrollment to the study. The expression of PD-L1 on M-MDSCS and MO/MA was assessed by flow cytometry. The profile of sPD-L1 was examined with ELISA. The expression of PD-L1 in mononuclear cells (MCs) was analyzed using real time PCR. PD-L1 immunohistochemical analysis was prepared on TC and IC. An in silico validation of prognostic significance of PD-L1 mRNA expression was performed based microarray datasets. Results OC patients had significantly higher frequency of MO/MA versus M-MDSC in the blood, ascites and tumour (each p 0.05). Significantly higher accumulation of blood-circulating M-MDSC, MO/MA, PD-L1+M-MDSC, PD-L1+MO/MA and sPD-L1 was observed in patients versus control (p 0.05). The expression of PD-L1 was significantly higher on IC versus TC (p 0.05) except higher level of PD-L1+TC in the endometrioid versus mucinous tumours. Interestingly, blood-circulating sPD-L1 positively correlated with PD-L1+M-MDSCs (p = 0.03) and PD-L1+MO/MA (p = 0.02) in the blood but not with these cells in the ascites and tumours nor with PD-L1+TC/IC (each p > 0.05). PD-L1 and sPD-L1 were not predictors of overall survival (OS; each p > 0.05). Further validation revealed no association between PD-L1 mRNA expression and OS in large independent OC patient cohort (n = 655, p > 0.05). Conclusions Although PD-L1 may not be a prognostic factor for OC, our study demonstrated impaired immunity manifested by up-regulation of PD-L1/sPD-L1. Furthermore, there was a positive association between PD-L1+ myeloid cells and sPD-L1 in the blood, suggesting that sPD-L1 may be a noninvasive surrogate marker for PD-L1+myeloid cells immunomonitoring in OC. Overall, these data should be under consideration during future clinical studies/trials. |
| نوع الوثيقة: |
article |
| وصف الملف: |
electronic resource |
| اللغة: |
English |
| تدمد: |
1479-5876 |
| Relation: |
http://link.springer.com/article/10.1186/s12967-020-02389-7; https://doaj.org/toc/1479-5876 |
| DOI: |
10.1186/s12967-020-02389-7 |
| URL الوصول: |
https://doaj.org/article/09e0ea1e3ac0445e9da4046a5d38a45d |
| رقم الانضمام: |
edsdoj.09e0ea1e3ac0445e9da4046a5d38a45d |
| قاعدة البيانات: |
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