Dataset Information

Accumulation of blood-circulating PD-L1-expressing M-MDSCs and monocytes/macrophages in pretreatment ovarian cancer patients is associated with soluble PD-L1.

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.

SUBMITTER: Okla K

PROVIDER: S-EPMC7268341 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Publications

Accumulation of blood-circulating PD-L1-expressing M-MDSCs and monocytes/macrophages in pretreatment ovarian cancer patients is associated with soluble PD-L1.

Okła Karolina K Rajtak Alicja A Czerwonka Arkadiusz A Bobiński Marcin M Wawruszak Anna A Tarkowski Rafał R Bednarek Wiesława W Szumiło Justyna J Kotarski Jan J

Journal of translational medicine 20200601 1

<h4>Background</h4>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.<h4>Methods</h4>The group of 74 pretreatment women were ...[more]

PMID: 32487171

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Dataset Information

Accumulation of blood-circulating PD-L1-expressing M-MDSCs and monocytes/macrophages in pretreatment ovarian cancer patients is associated with soluble PD-L1.

Background

Methods

Results

Conclusions

Publications

Accumulation of blood-circulating PD-L1-expressing M-MDSCs and monocytes/macrophages in pretreatment ovarian cancer patients is associated with soluble PD-L1.

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