Protein expression of programmed death 1 ligand 1 and ligand 2 independently predict poor prognosis in surgically resected lung adenocarcinoma

Zhang, Yang; Wang, Lei; Li, Yuan; Pan, Yunjian; Wang, Rui; Hu, Haichuan; Li, Hang; Luo, Xiangyang; Ye, Ting; Sun, Yihua; Chen, Hai Quan

doi:10.2147/ott.s59959

Cited by 191 publications

(166 citation statements)

References 27 publications

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“…Although PD-L1 expression was not revealed as a prognostic factor in our study, 2 of 6 studies of NSCLC showed that it was a negative prognostic factor [24,25] , an additional 2 studies showed that it was a positive prognostic factor [26,27] , and 3 studies showed that it had no prognostic value [28,29] ; therefore, the prognostic relevance of PD-L1 expression in NSCLC is controversial. However, it should be considered that these studies used non-standardized methods to assess PD-L1 expression, including different PD-L1 antibodies and relatively small sample sizes.…”

Section: Discussioncontrasting

confidence: 69%

Impact of PD-L1 Expression in Patients with Surgically Resected Non-Small-Cell Lung Cancer

Igawa

Sato²,

Ryuge³

et al. 2017

Oncology

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Background: Immunotherapy can become a crucial therapeutic option to improve the prognosis of patients with non-small-cell lung cancer (NSCLC). Here, we evaluated the impact of programmed cell death ligand-1 (PD-L1) expression in surgically resected NSCLCs. Methods: We estimated PD-L1 expression in 229 consecutive NSCLC specimens using rabbit polyclonal antibodies to human PD-L1 in a SP263 immunohistochemical assay and evaluated PD-L1 expression for potential associations with clinicopathological parameters and survival time. Results: PD-L1 expression was significantly higher in tumors from men or current smokers. Squamous cell carcinoma histology was independently associated with high PD-L1 expression according to multivariate analysis (p = 0.015). The 5-year survival rate of patients was 70%, and the difference in the 5-year survival rate according to PD-L1 expression was not statistically significant (high expression group [67%] vs. low expression group [68%]); however, the squamous cell carcinoma group exhibited significantly lower 5-year survival rates as compared to the non-squamous cell carcinoma group (53 and 71%, respectively; p = 0.026). Conclusion: Here, we revealed high PD-L1 expression and poor prognosis observed in patients with surgically resected squamous NSCLC as compared with non-squamous NSCLC. Our results support the identification of patient subsets that most likely respond to anti-PD-1 therapy as the first step in precision medicine.

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Section: Discussioncontrasting

confidence: 69%

Impact of PD-L1 Expression in Patients with Surgically Resected Non-Small-Cell Lung Cancer

Igawa

Sato²,

Ryuge³

et al. 2017

Oncology

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“…[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: 67%

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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“…PD-L1 is not expressed by normal epithelial tissues, normal lymph nodes, and plasma cells, but it is aberrantly expressed on various human cancers, lymphoma cells, and myeloma cells [13][14][15]. PD-L1 may promote Ca progression by disabling the host antitumor response, and its expression on tumor cells is associated with poor prognosis in various malignant tumors including renal cell cancer, breast cancer, pancreas cancer, ovarian cancer, gastric cancer, esophageal cancer, head and neck cancer, and non-small cell lung cancer [16][17][18][19][20][21][22]. PD-L1 has an important role in lymphomagenesis.…”

Section: Discussionmentioning

confidence: 99%

Programmed death-1 (PD-1), programmed death-ligand 1 (PD-L1), and EBV-encoded RNA (EBER) expression in Hodgkin lymphoma

et al. 2015

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Programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) are new targets in cancer immunotherapy. PD-1 protein is an immune checkpoint expressed in many tumors. Epstein-Barr virus (EBV) is present in malignant Hodgkin/Reed-Sternberg (HRS) cells in approximately 40-50 % of Hodgkin lymphoma (HL). The aim of this study is to evaluate the clinical and prognostic importance of PD-1 and/or PD-L1 in HL and also to determine the association between EBV-encoded RNA (EBER) and PD-1/PD-L1. Formalin-fixed, paraffin-embedded tissue samples from 87 cases with HL were analyzed in this study. Immunohistochemical staining was performed to detect the PD-1 and PD-L1 expressions. Chromogenic in situ hybridization for EBER was performed using fluorescein-labeled oligonucleotide probes. PD-1 and PD-L1 expressions were found in 20 % of the cases. The EBER positivity was found in 40 cases (45 %). It has been found that co-expression of PD-1 and PD-L1 was associated with shorter survival although PD-1 or PD-L1 expressions were not found to be related with survival. Overall survival (OS) and disease-free survival (DFS) in cases without PD-1 and PD-L1 expressions were 135 and 107 months, respectively. OS and DFS in cases with co-expression for PD-1 and PD-L1 were 24 and 20 months, respectively, and these differences were found to be statistically significant for both OS and DFS (p = 0.002 and p = 0.003, respectively). Cox regression analysis showed that co-expression of PD-1 and PD-L1 was found to be an independent risk factor for prognosis (OR 6.9, 95 % CI 1.9-24.3). Targeting PD-1 and/or PD-L1 is meaningful due to the 20 % expression of each in HL, and we did not find an important association between PD-1 and PD-L1 and EBER expression in HL. Very poor outcome in cases with co-expression of PD-1/PD-L1 suggests new avenues to detect the new prognostic markers and also therapeutic approaches in HL.

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Protein expression of programmed death 1 ligand 1 and ligand 2 independently predict poor prognosis in surgically resected lung adenocarcinoma

Cited by 191 publications

References 27 publications

Impact of PD-L1 Expression in Patients with Surgically Resected Non-Small-Cell Lung Cancer

Impact of PD-L1 Expression in Patients with Surgically Resected Non-Small-Cell Lung Cancer

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

Programmed death-1 (PD-1), programmed death-ligand 1 (PD-L1), and EBV-encoded RNA (EBER) expression in Hodgkin lymphoma

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