Programmed cell death-ligand 1 expression is associated with a favourable immune microenvironment and better overall survival in stage I pulmonary squamous cell carcinoma

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

doi:10.1016/j.ejca.2015.12.033

Cited by 118 publications

(98 citation statements)

References 54 publications

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“…Similarly, we found that the DFS and OS were not significantly different between the positive and negative PD-L1 expression in TILs groups. In addition, correlation between PD-L1 expression in TCs and TILs has been shown in SCC and ADC, but our study did not find this correlation in primary pulmonary LELC (9,19).…”

Section: Discussioncontrasting

confidence: 82%

“…In recent years, up-regulated PD-L1 expression in TILs has been detected in many malignant solid tumors, and its potential predictive value for anti-PD-1/PD-L1 immune therapy and survival outcomes has also been reported. However, the scant reports from Yang et al and Cha et al revealed no evidence supporting the application of PD-L1 expression in TILs as a prognostic factor for NSCLC (9,19). Similarly, we found that the DFS and OS were not significantly different between the positive and negative PD-L1 expression in TILs groups.…”

Section: Discussioncontrasting

confidence: 68%

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Correlation and prognostic significance of PD-L1 and P53 expression in resected primary pulmonary lymphoepithelioma-like carcinoma

Zhang

Wang

et al. 2018

J. Thorac. Dis.

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Background: Aberrant expression of programmed cell death-ligand 1 (PD-L1) and protein 53 (P53) has been observed in various malignancies, and recently, the mechanism of PD-L1 regulation by P53 has been elucidated. We aimed to explore possible correlations between PD-L1 and P53 expression and the prognosis of patients with resected pulmonary lymphoepithelioma-like carcinoma (LELC). Methods: A total of 67 consecutive patients with primary pulmonary LELC who underwent radical resection from January 2003 to December 2014 were enrolled in our study. Membranous PD-L1 and nuclear P53 expression were detected by immunohistochemical staining (IHC). Results: Positive expression of PD-L1 in tumor cells (TCs), PD-L1 in tumor-infiltrating lymphocytes (TILs) and P53 was investigated in 44 patients (65.7%), 37 patients (55.2%), and 34 patients (50.7%), respectively. Using univariate and multivariable analysis, both PD-L1 (+) in TCs and P53 (+) were observed to be significantly independent prognostic factors associated with longer disease-free survival (DFS, P=0.037 and 0.039, respectively), along with early stage LELC (P=0.037), but had no association with overall survival (OS) (P>0.05). In the P53 (+) group, the rate of patients with PD-L1 (+) in TCs was significantly higher than in the P53 (−) group (85.3% vs. 45.5%, P=0.001). In addition, among the 45 patients who underwent adjuvant chemotherapy, DFS was significantly longer in patients with either PD-L1 (+) in TCs or P53 (+) (P=0.036 and 0.044, respectively).Conclusions: PD-L1 and P53 may be potential therapeutic targets for primary pulmonary LELC. PD-L1 (+) in TCs and P53 (+) were reliable predictors for longer DFS and benefits from adjuvant therapy in resected cases. Routine detection of these two indices in lung LELC may be warranted.

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Section: Discussioncontrasting

confidence: 82%

Section: Discussioncontrasting

confidence: 68%

Correlation and prognostic significance of PD-L1 and P53 expression in resected primary pulmonary lymphoepithelioma-like carcinoma

Zhang

Wang

et al. 2018

J. Thorac. Dis.

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“…IHC testing has yet to be standardized and optimal IHC assays have not been validated. The IHC antibody we used was also utilized in several studies on various neoplasms, including lymphoma, [27] lung cancer, [6, 16, 19, 28, 29] and head and neck cancer [17]. The cut-off value of 5% seemed to be a reasonable threshold for PD-L1 expression with our IHC antibody.…”

Section: Discussionmentioning

confidence: 99%

High PD-L1 expression is associated with stage IV disease and poorer overall survival in 186 cases of small cell lung cancers

et al. 2017

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BackgroundSmall cell lung cancer (SCLC) is an aggressive malignancy with a distinct natural history and dismal prognosis. SCLC is characterized as a recalcitrant neoplasm with limited therapeutic options and platinum-based chemotherapy is the treatment of choice. Programmed cell death-ligand 1(PD-L1)-mediated immune escape may be a suitable target for specific therapy, but its role in SCLC is unclear.Materials and methodsIn total, 186 SCLC cases were investigated. Paraffin-embedded tumor sections were stained with a PD-L1 antibody. PD-L1 overexpression was denoted by moderate-to-strong PD-L1 membrane staining in ≥ 5% of tumor cells. Tumor cells and infiltrating lymphocytes were scored separately.ResultsThe overall frequency of PD-L1 overexpression, in tumor cells and tumor infiltrating lymphocytes (TILs) was 78.0% and 54.3%, respectively. High tumor PD-L1 expression was significantly correlated with high TIL PD-L1 expression (P=0.001) and stage IV disease (P=0.048). Multivariate analysis revealed that high tumor PD-L1 expression and stage IV disease were two independent risk factors for poor overall survival.ConclusionsHigh PD-L1 expression was observed in SCLCs compared with their expression in conventional NSCLCs. The aggressive behavior of SCLC could be partially related to PD-L1-mediated immune escape. High PD-L1 expression correlated with poor prognosis and may provide a rationale for immunotherapy for high-grade SCLC.

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“…1a) and a score of less than 5% as 'PD-L1-negative' (Fig. 1b) based on recent studies of tumor PD-L1 expression (15,21,34). A random subset of 126 cases were blindly examined by a second pathologist (YY).…”

Section: Immunohistochemistry For Pd-l1mentioning

confidence: 99%

Relationship of tumor PD-L1 expression withEGFRwild-type status and poor prognosis in lung adenocarcinoma

Inamura

Yokouchi

Sakakibara

et al. 2016

Jpn. J. Clin. Oncol.

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Background: Programmed death-ligand 1 is an immune modulator that promotes immunosuppression by binding to programmed death-1 of T-lymphocytes. Whereas programmed death-ligand 1 expression has been shown to be associated with the clinical response to anti-programmed death-ligand 1 antibody, the association of tumor programmed death-ligand 1 expression with clinicopathological/molecular features and with prognosis remains inconclusive in lung adenocarcinoma. We therefore examined the association of programmed death-ligand 1 expression with the clinicopathological/molecular features and prognosis of lung adenocarcinoma. Methods: Using tissue microarrays of 268 consecutive cases of lung adenocarcinoma, we evaluated programmed death-ligand 1 expression by immunohistochemistry. We examined the association of programmed death-ligand 1 expression with clinicopathological and molecular features. We also examined the prognostic association of programmed death-ligand 1 expression, using the log-rank test as well as Cox proportional hazards regression models to compute the mortality hazard ratio (HR). Results: Programmed death-ligand 1 immunoreactivity (at least 5% of the tumor cells) was observed in 43 (16%) of 268 cases of lung adenocarcinoma. Programmed death-ligand 1 positivity was associated with less tumor differentiation (P < 0.0001) and EGFR wild-type status (P = 0.0008). In a multivariable logistic regression analysis, less tumor differentiation was independently associated with programmed death-ligand 1 positivity (multivariable odds ratio, 6.54; 95% confidence interval [CI], 2.37-23.3; P = 0.0001). Programmed death-ligand 1 positivity was associated with a poor prognosis for lung cancer-specific survival (log-rank, P = 0.019; HR, 1.73; 95% CI, 1.06-2.72; P = 0.030) and overall survival (log-rank, P = 0.0014; HR, 1.88; 95% CI, 1.25-2.74). Conclusion: Our study demonstrated that programmed death-ligand 1 positivity in lung adenocarcinoma was associated with less tumor differentiation and EGFR wild-type status, as well as a poor prognosis.

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Programmed cell death-ligand 1 expression is associated with a favourable immune microenvironment and better overall survival in stage I pulmonary squamous cell carcinoma

Cited by 118 publications

References 54 publications

Correlation and prognostic significance of PD-L1 and P53 expression in resected primary pulmonary lymphoepithelioma-like carcinoma

Correlation and prognostic significance of PD-L1 and P53 expression in resected primary pulmonary lymphoepithelioma-like carcinoma

High PD-L1 expression is associated with stage IV disease and poorer overall survival in 186 cases of small cell lung cancers

Relationship of tumor PD-L1 expression withEGFRwild-type status and poor prognosis in lung adenocarcinoma

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