Expression of PD-L1 in ovarian cancer and its synergistic antitumor effect with PARP inhibitor

Xue, Chunyan; Xu, Yun; Ye, Wenfeng; Xie, Quanqin; Gao, Hongyan; Xu, Bin; Zhang, Dachuan; Jiang, Jingting

doi:10.1016/j.ygyno.2019.12.012

Cited by 37 publications

(28 citation statements)

References 22 publications

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“… 16 Additionally, PD-L1 expression was negatively correlated with CD8 + T cell counts and inhibited the function of CD8 + T cells. 15 Likewise, Schachtele et al. 28 proposed that CD8 + T lymphocytes are negatively regulated by PD-L1 in viral encephalitis, which was partially consistent with the observations of our study.…”

Section: Discussionsupporting

confidence: 92%

“…Previous literature has suggested that reduction or apoptosis of CD8 + T cells contributes to immune escape. 15 , 16 To evaluate the immune escape of OC cells, CD8 + T cells were co-cultured with the above-treated SKOV3 or A2780 cells. Flow cytometry was performed to detect the expression of PD-L1 in CD8 + T cells as well as the CD8 + T cell apoptosis rate.…”

Section: Resultsmentioning

confidence: 99%

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TAM-derived extracellular vesicles containing microRNA-29a-3p explain the deterioration of ovarian cancer

Ling

Ruan

2021

Molecular Therapy - Nucleic Acids

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Extracellular vesicles (EVs) secreted from tumor-associated macrophages (TAMs) are known to generate an immune-suppressive environment conducive to the development of ovarian cancer (OC). We tried to elucidate the role of TAM-derived exosomal microRNA (miR)-29a-3p in OC. miR-29a-3p, forkhead box protein O3 (FOXO3), and programmed death ligand-1 (PD-L1) expression was determined and their interactions evaluated. EVs were isolated, followed by determination of the uptake of EVs by OC cells, after which the proliferation and immune escape facilities of the OC cells were determined. OC xenograft models were constructed with EVs in correspondence with in vivo experiments. Overexpressed miR-29a-3p was detected in OC, and miR-29a-3p promoted OC cell proliferation and immune escape. EVs derived from TAMs enhanced the proliferation of OC cells. miR-29a-3p was enriched in TAM-EVs, and TAM-EVs delivered miR-29a-3p into OC cells. Downregulated FOXO3 was identified in OC, whereas miR-29a-3p targeted FOXO3 to suppress glycogen synthase kinase 3β (GSK3β) activity via the serine/threonine protein kinase (AKT)/GSK3β pathway. Inhibition of TAM-derived exosomal miR-29a-3p decreased PD-L1 to inhibit OC progression through the FOXO3-AKT/GSK3β pathway in vitro and in vivo . Taken together, the current studies highlight the FOXO3-AKT/GSK3β pathway and the mechanism by which TAM-derived exosomal miR-29a-3p enhances the expression of PD-L1 to facilitate OC cell proliferation and immune escape.

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Section: Discussionsupporting

confidence: 92%

Section: Resultsmentioning

confidence: 99%

TAM-derived extracellular vesicles containing microRNA-29a-3p explain the deterioration of ovarian cancer

Ling

Ruan

2021

Molecular Therapy - Nucleic Acids

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“…This information could suggest an interest in combining PD1/PD-L1 inhibitor and PARP inhibitor treatment. 42 In breast cancer, it has been demonstrated that two-thirds of patients with PD-L1 positive tumors have a high response to targeted therapy but also 16.7 % of PD-L1 negative patients. 43 The ongoing "ATALANTE" trial is investigating the efficacy of atezolizumab compared to placebo in patients with PD-L1 positive OC compared to PD-L1 negative patients.…”

Section: Discussionmentioning

confidence: 99%

PD-L1 expression with QR1 and E1L3N antibodies according to histological ovarian cancer subtype: A series of 232 cases

et al. 2021

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Therapeutic strategies for epithelial ovarian cancers are evolving with the advent of immunotherapy, such as PD-L1 inhibitors, with encouraging results. However, little data are available on PDL-1 expression in ovarian cancers. Thus, we set out to determine the PD-L1 expression according to histological subtype. We evaluated the expression of two PD-L1 clones – QR1 and E1L3N – with two scores, one based on the percentage of labeled tumor cells (tumor proportion score, TPS) and the other on labeled immune cells (combined proportion score, CPS) in a consecutive retrospective series of 232 ovarian cancers. PD-L1 expression was more frequent in high grade serous carcinoma (27.5% with E1L3N clone and 41.5% with QR1 clone), grade 3 endometrioid carcinoma (25% with E1L3N clone and 50% with QR1 clone), and clear-cell carcinomas (27.3% with E1L3N clone and 29.6% with QR1 clone) than other histological subtypes with CPS score. Using the CPS score, 17% of cases were labeled with E1L3N vs 28% with QR1. Using the TPS score, 14% of cases were positive to E1L3N vs 17% for QR1. For TPS and CPS, respectively, 77% and 78% of the QR1 cases were concordant with E1L3N for the thresholds of 1%. Overall and progression-free survival between PD-L1 positive and PD-L1 negative patients were not different across all histological types, and each subtype in particular for serous carcinomas expressing PD-L1. Expression of PD-L1 is relatively uncommon in epithelium ovarian tumors. When positive, usually <10% of tumor cells are labeled. QR1 clone and CPS appear the best tools to evaluate PD-L1 expression.

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“…For example, Pd-L1 is upregulated in human osteosarcoma tissues and increases cell invasion (30). Moreover, high expression of Pd-L1 affects the survival and prognosis of patients with ovarian cancer (31). Zuo et al (32) reported that Pd-L1 silencing suppressed chemoresistance of ddP-resistant ovarian cancer cells to ddP, as evidenced by inhibited proliferation, G1-phase cell cycle arrest and promotion of apoptosis.…”

Section: Discussionmentioning

confidence: 99%

FGD5‑AS1 promotes cisplatin resistance of human lung adenocarcinoma cell via the miR‑142‑5p/PD‑L1 axis

et al. 2020

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Previous studies have reported that long non-coding (lnc) RNA FGD5-antisense 1 (FGD5-AS1) promotes tumor proliferation, migration and invasion. Therefore, the present study aimed to elucidate the biological role and underlying molecular mechanisms of FGD5-AS1 in cisplatin (DDP) resistance of lung adenocarcinoma (LAD) cells. The results demonstrated that FGD5-AS1 was highly expressed in DDP-resistant LAD tissues and cells. Knockdown of FGD5-AS1 decreased the proliferative, migratory and invasive abilities of DDP-resistant LAD cells. Moreover, it was identified that FGD5-AS1 acted as a molecular sponge for microRNA (miR)-142, and FGD5-AS1 enhanced the resistance of A549/DDP cells to DDP by directly interacting with miR-142. Programmed cell death 1 ligand 1 (PD-L1) was also found to be a key effector of the FGD5-AS1/miR-142 axis to regulate the chemoresistance of DDP-resistant LAD cells. In conclusion, the present study demonstrated that FGD5-AS1 increased DDP resistance of LAD via the miR-142/PD-L1 axis, which may offer a novel treatment strategy for patients with DDP-resistant LAD.

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Expression of PD-L1 in ovarian cancer and its synergistic antitumor effect with PARP inhibitor

Cited by 37 publications

References 22 publications

TAM-derived extracellular vesicles containing microRNA-29a-3p explain the deterioration of ovarian cancer

TAM-derived extracellular vesicles containing microRNA-29a-3p explain the deterioration of ovarian cancer

PD-L1 expression with QR1 and E1L3N antibodies according to histological ovarian cancer subtype: A series of 232 cases

FGD5‑AS1 promotes cisplatin resistance of human lung adenocarcinoma cell via the miR‑142‑5p/PD‑L1 axis

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