Programmed cell death-ligand 1 expression in surgically resected stage I pulmonary adenocarcinoma and its correlation with driver mutations and clinical outcomes

Yang, Ching‐Yao; Lin, Mong-Wei; Chang, Yih‐Leong; Wu, Chen-Tu; Yang, Pan‐Chyr

doi:10.1016/j.ejca.2014.01.018

Cited by 268 publications

(252 citation statements)

References 31 publications

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“…The expression rate of PD-L1 in pulmonary adenocarcinomas was ∼ 60%, and this was higher compared with several previous studies, 20,25 but lower compared with a very recent study. 22 This might be attributable to the use of different antibodies and interpretation criteria in the lack of consensus PD-L1 immunohistochemistry method at present.…”

Section: Discussioncontrasting

confidence: 69%

“…15,37 However, it has also been reported that PD-L1 expression was not associated with EGFR, KRAS, or BRAF mutation or ALK translocation. 20 In contrast, other studies reported that PD-L1 overexpression was associated with EGFR mutation in non-small-cell lung cancer. 21,22 In this study, although a strong expression of PD-L1 was more common in pulmonary adenocarcinomas with wild-type EGFR, there was overall no significant difference in PD-L1 expression according to EGFR mutation status.…”

Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

“…[20][21][22]25 However, only a few studies performed analysis on the PD-L1 expression according to the histologic classification of pulmonary adenocarcinomas using IASLC/ATS/ERS (2011) system. 20,33 Our study showed that PD-L1, but not PD-L2, expression was significantly and independently associated with histologic grades of pulmonary adenocarcinomas. Given that poorly differentiated pulmonary adenocarcinomas usually show more aggressive behavior than well-differentiated ones and PD-L1 expression in tumor cells may exert immune evasion of cancers, it is suggested that high PD-L1 expression may be one of the candidates to explain progression and aggressive biologic behavior of pulmonary adenocarcinomas with poor differentiation.…”

Section: Discussionmentioning

confidence: 99%

“…However, these results were conflicting. [20][21][22] Thus, we addressed this issue in this study using a large cohort. Our study demonstrated that PD-L1 and PD-L2 expression varied with the histology and genetic alteration status and that PD-L1 expression and a high ratio of PD-1 + /CD8 + tumor-infiltrating lymphocytes were prognostic factors associated with poor outcomes in patients with pulmonary adenocarcinoma.…”

mentioning

confidence: 99%

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Clinicopathologic analysis of programmed cell death-1 and programmed cell death-ligand 1 and 2 expressions in pulmonary adenocarcinoma: comparison with histology and driver oncogenic alteration status

et al. 2015

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Immunotherapies targeting the programmed cell death-1/programmed cell death-ligand 1 pathway have emerged as promising therapeutic strategies for lung cancer. However, the expression pattern and prognostic implications of programmed cell death-ligand 1 and 2 and programmed cell death-1 in comparison with the histology and genetic alterations in pulmonary adenocarcinomas remains unclear and thus were addressed here. Programmed cell death-ligand 1 and 2 expression in tumor cells and the quantities of programmed cell death-1 + and CD8 + tumor-infiltrating lymphocytes were immunohistochemically evaluated in 497 resected pulmonary adenocarcinomas and analyzed according to clinicopathological and genetic statuses. Programmed cell death-ligand 1 and 2 expression were observed in 59% and 64% of pulmonary adenocarcinomas, respectively, and showed a strong positive correlation with each other (Po 0.001). Programmed cell death-ligand 1 expression was higher in nodal metastasis cases (P = 0.006), smokers (P = 0.056), poorly differentiated tumors and histologic subtypes of solid and micropapillary patterns (Po0.001). There was no significant difference in programmed cell death-ligand 1 and 2 expression according to EGFR mutation status. However, programmed cell death-ligand 1 expression was correlated with ALK translocation (P = 0.054) and expression of EGFR and MET (Po 0.001). Meanwhile, programmed cell death-ligand 2 expression was correlated with ALK translocation (P = 0.052), and expression of MET (Po 0.001) and ERBB2 (P = 0.013). The numbers of CD8 + and programmed cell death-1 + lymphocytes were higher in smokers (P = 0.012 and 0.016) and MET-expressing adenocarcinomas (Po 0.001). Patients expressing programmed cell death-ligand 1 and/or high ratios of programmed cell death-1 + /CD8 + lymphocytes showed shorter disease-free survival (P = 0.001). Our study demonstrated that programmed cell death-ligand 1 and 2 expression varied with histology, EGFR, ALK, MET, and ERBB2 statuses, and activation of the programmed cell death-1/programmed cell death-ligand 1 pathway may be a poor prognostic factor in pulmonary adenocarcinomas.

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Section: Discussioncontrasting

confidence: 69%

Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Clinicopathologic analysis of programmed cell death-1 and programmed cell death-ligand 1 and 2 expressions in pulmonary adenocarcinoma: comparison with histology and driver oncogenic alteration status

et al. 2015

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Biomarkers for the Clinical Use of PD-1/PD-L1 Inhibitors in Non–Small-Cell Lung Cancer

2016

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The refinement of existing biomarkers and identification of novel predictive biomarkers will be key to ensuring the effective and safe use of these agents. Since most patients still do not benefit from these agents, it is critical to continue to work to define the select patient population who will derive durable benefit from PD-1/PD-L1 inhibition and identify markers that could have predictive value for combination therapies that could expand the population who benefit.

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MicroRNA‐155‐5p suppresses PD‐L1 expression in lung adenocarcinoma

et al. 2020

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MiR‐155‐5p is a key oncogenic microRNA that maintains immune homeostasis and mediates cross‐talk between inflammation and tumorigenesis. High expression of programmed death ligand‐1 (PD‐L1) also plays an important role in immune tolerance in tumors. The present study aimed to explore the relationship between miR‐155‐5p and PD‐L1 in lung adenocarcinoma (LUAD) cells A549 and H1650. The expression levels of miR‐155‐5p and PD‐L1 in LUAD patients were detected by a quantitative reverse transcriptase‐polymerase chain reaction (qRT‐PCR) and mimics of miR‐155‐5p were used to model increased expression in A549 or H1650 cells. After 24 h, we measured levels of PD‐L1 by qRT‐PCR, western blotting and flow cytometry. In addition, we identified two sites in the PD‐L1 3′‐UTR (5′‐AGCAUUA‐3′ and 5′‐GCAUUAA‐3′) that can be bound by miR‐155‐5p using TargetScan (http://www.targetscan.org). Compared to normal tissue, miR‐155‐5p was overexpressed in tumor tissue (P = 0.0456), whereas the expression of PD‐L1 was not significantly different (P = 0.1349). The expression levels of miR‐155‐5p and PD‐L1 were negatively correlated (r = −0.6409, P = 0.0459 and r = −0.7544, P = 0.0117). Exogenous overexpression of miR‐155‐5p decreased the mRNA, total protein and membrane protein expression levels of PD‐L1 both in A549 and H1650 cells (P < 0.05). Taken together, our data suggest that miR‐155‐5p may suppress the expression of PD‐L1 in LUAD.

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Programmed cell death-ligand 1 expression in surgically resected stage I pulmonary adenocarcinoma and its correlation with driver mutations and clinical outcomes

Cited by 268 publications

References 31 publications

Clinicopathologic analysis of programmed cell death-1 and programmed cell death-ligand 1 and 2 expressions in pulmonary adenocarcinoma: comparison with histology and driver oncogenic alteration status

Clinicopathologic analysis of programmed cell death-1 and programmed cell death-ligand 1 and 2 expressions in pulmonary adenocarcinoma: comparison with histology and driver oncogenic alteration status

Biomarkers for the Clinical Use of PD-1/PD-L1 Inhibitors in Non–Small-Cell Lung Cancer

MicroRNA‐155‐5p suppresses PD‐L1 expression in lung adenocarcinoma

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