Prognostic value of PD-L1 in esophageal squamous cell carcinoma: a meta-analysis

Guo, Wei; Wang, Pan; Li, Ning; Shao, Fei; Zhang, Hao; Yang, Zhenlin; Li, Renda; Gao, Yibo; He, Jie

doi:10.18632/oncotarget.23810

Cited by 69 publications

(50 citation statements)

References 56 publications

(55 reference statements)

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“…PD‐L1 expression in TCs impairs T‐cell regulation, disrupts the antitumoral immune response, and contributes to an immunosuppressive microenvironment, allowing tumour immune escape . In several cancer types, such as HNSCC, oropharyngeal squamous cell carcinoma (SCC), pulmonary adenocarcinoma, oesophageal SCC, and urothelial carcinoma, PD‐L1 immunoexpression has been reported to be associated with advanced tumour stage, poor clinical outcome, and/or decreased overall survival. Similarly, in a cohort of 219 salivary gland carcinomas of various types, including 31 SDCs, Mukaigawa et al .…”

Section: Discussionmentioning

confidence: 99%

“…[29][30][31][32] In the present study, we investigated the immune environment in SDC, which is an an aggressive high-grade salivary malignancy, focusing on the immunoexpression of PD-L1, PD-1, the CTA PRAME, and MHC I. PD-L1 expression in TCs impairs T-cell regulation, disrupts the antitumoral immune response, and contributes to an immunosuppressive microenvironment, allowing tumour immune escape. 1,[33][34][35][36] In several cancer types, such as HNSCC, 12 oropharyngeal squamous cell carcinoma (SCC), 37 pulmonary adenocarcinoma, 38 oesophageal SCC, 39 and urothelial carcinoma, 40 PD-L1 immunoexpression has been reported to be associated with advanced tumour stage, poor clinical outcome, and/or decreased overall survival. Similarly, in a cohort of 219 salivary gland carcinomas of various types, including 31 SDCs, Mukaigawa et al reported that a high level of PD-L1 expression in TCs was associated with poor overall survival, DSS, and DFS.…”

Section: Discussionmentioning

confidence: 99%

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The immune microenvironment and expression of PD‐L1, PD‐1, PRAME and MHC I in salivary duct carcinoma

Jungbluth

Frosina

et al. 2019

Histopathology

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Aims Salivary duct carcinoma (SDC) is an aggressive salivary malignancy that results in high mortality rates and is often resistant to chemotherapy. Anti‐programmed death‐1 (PD‐1)/programmed death ligand‐1 (PD‐L1) checkpoint inhibitors have led to dramatic improvements in patients with various cancers. Other immunotherapeutic approaches, e.g. cancer vaccines, have shown promising results. Cancer testis antigens, e.g. preferentially expressed antigen in melanoma (PRAME), are regarded as promising vaccine targets because of their tumour‐specific expression pattern. Methods and results We analysed the immunoexpression of PD‐L1, PD‐1, major histocompatibility complex class I (MHC I) and PRAME in 53 SDCs. The immunoexpression levels of PD‐L1 in tumour cells (TCs) and immune cells (ICs), PD‐1 in ICs, PRAME in TCs and MHC I in TCs were analysed, and were correlated with outcome. PRAME expression was seen in 83% of SDCs. No PRAME staining was present in normal salivary gland tissue. With the three established diagnostic algorithms proposed for head and neck squamous cell carcinoma, the criteria being a combined positive score of ≥1, TC% ≥1%, and TC% ≥25%, 35 (66%), 17 (32%) and three cases (6%), respectively, were deemed to be positive for PD‐L1. PD‐1‐positive ICs were seen in 35 (66%) cases. MHC I down‐regulation was seen in 82% of SDCs. There was a significant correlation among PD‐L1 expression in ICs, PD‐1 expression in ICs, and PRAME expression in TCs. PD‐L1 expression in TCs and lack of PD‐1 expression in ICs were associated with decreased disease‐specific survival in SDC patients. Conclusions Alterations of the tumour immune microenvironment are common in SDCs, including expression of PD‐1/PD‐L1 and PRAME, which opens the way to potential novel immune therapies, such as cancer vaccination and PD‐1/PD‐L1 blockade, in these tumours.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The immune microenvironment and expression of PD‐L1, PD‐1, PRAME and MHC I in salivary duct carcinoma

Jungbluth

Frosina

et al. 2019

Histopathology

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“…The TME was before divided into four classifications according to the expression of PD-L1 in tumor cells and the presence of TILs [ 38 ], thus the expression of checkpoints was included into immunoscore studies. Previous studies reported the relationship between PD-L1+ tumors and poorer prognosis in ESCC [ 39 , 40 ], however, they did not consider the expression of PD-L1 in TCs or ICs separately. This is the first time to investigate whether PD-L1 expressed by different cells has different prognostic values in ESCC.…”

Section: Discussionmentioning

confidence: 99%

A nomogram-based immunoprofile predicts overall survival for previously untreated patients with esophageal squamous cell carcinoma after esophagectomy

Duan

Xie

et al. 2018

j. immunotherapy cancer

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BackgroundImmunoscore, as a prognostic tool defined to quantify in situ immune cell infiltrates, appears to be superior to the TNM staging system. In esophageal squamous cell carcinoma (ESCC), no immunoscore has been established; however, in situ tumor immunology is recognized as highly important. Our study aimed to construct a comprehensive immunoprofile for ESCC.MethodsThe infiltration of four immune cell types (CD8+/CD4+/Foxp3+/CD33+ cells), the expression of both inhibitory (PD-1/PD-L1/Tim-3/LAG-3) and stimulatory checkpoints (OX-40/ICOS), and IDO1 were evaluated by IHC staining and multi-color immunofluorescence in two independent cohorts (95 patients in the primary cohort and 55 patients in the validation cohort). The association with patients’ overall survival was analyzed by the Kaplan-Meier method and the Cox model. Nomogram-based immunoprofile was established using the independent prognostic variables. To determine its predictive accuracy and discriminatory capacity, the C-index and calibration curve were calculated.ResultsSignificant correlation of PD-L1 expression in tumor cells with PD-1+ T cell infiltration was found (P = 0.035), indicating the activation of the inhibitory PD-1/PD-L1 pathway in ESCC cases. More PD-L1+ ICs, Tim-3+ ICs and LAG-3+ ICs were found in the CD8-rich tumor microenvironment, which is in accordance with the feedback nature of immune system. After adjustment by TNM stage, four immune variables including the infiltration of CD8+/Foxp3+/CD33+ cells and the PD-L1 expression by tumor cells were selected to construct a prognostic nomogram. The calibration curves showed good accuracy of the nomogram for survival prediction. To overcome the complexity of applying a nomogram in a clinical setting, a simple immunoprofile was then established according to the points of each factor from the nomogram. Our immunoprofile model could separate same-stage patients into different risk subgroups, and showed superior accuracy for survival prediction than the TNM staging system based on the C-index calculation and ROC analysis.ConclusionsOur nomogram-based immunoprofile can provide more accurate prognosis prediction and is an important complement to the TNM staging system for operable ESCC patients.Electronic supplementary materialThe online version of this article (10.1186/s40425-018-0418-7) contains supplementary material, which is available to authorized users.

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“…However, it cannot be ignored that some patients with tumours negative for PD-L1 also show a clinical response when treated with PD1/PD-L1 inhibitors (29). The strikingly heterogeneous PD-L1 expression in different PD-L1 IHC assays of the same tumour tissue may lead to the misclassi cation of patients who could be treated with PD1/PD-L1 inhibitors (30). In this regard, we attempted to assess the correlation and differences between the expression scores obtained by the SP263 and 22C3 assays.…”

Section: Discussionmentioning

confidence: 99%

PD-L1 Expression in Esophageal Squamous Cell Carcinoma: A Comparative Analysis of 3 Different Antibodies

Guo

et al. 2020

Preprint

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Background: Several studies have assessed the comparability of various immunohistochemical assays for programmed cell death 1 ligand 1 (PD-L1) expression in different kinds of tumours. However, there is a lack of relevant research on the detection efficacy of different PD-L1 clones in esophageal squamous cell carcinoma (ESCC). This study was performed to compare the PD-L1 expression results of three PD-L1 antibodies to assess their effectiveness.Methods: Three hundred and twenty-four cases of ESCC tissues in our medical institution were used to prepare tissue microarrays (TMAs). TMAs were stained with three validated assays (Ventana’s SP263 and Dako’s 28-8 and 22C3). Then, pathologists scored each tissue according to PD-L1 staining.Results: We found very high concordance when comparing 28-8 with SP263 at both the 1% (95.7%) and 50% (99.1%) cutoffs. Low overall concordance was found between 28-8 and 22C3 at the 1% cutoff (85.5%). Moreover, sensitivities of 91.2% and 87.5% were found for 28-8 compared with SP263 at the 1% and 50% cutoffs, respectively. Sensitivities of only 75.6% and 50% were found for 28-8 compared with 22C3 at the 1% and 50% cutoffs, respectively, which may result in more false negatives.Conclusions: We demonstrate that the PD-L1 SP263 shows high levels of overall agreement with 28-8 and relatively high sensitivity, with a low false negative rate. Thus, SP263 seems to be a reliable assay for PD-L1 testing in ESCC when considering pembrolizumab as immunotherapy.

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Prognostic value of PD-L1 in esophageal squamous cell carcinoma: a meta-analysis

Cited by 69 publications

References 56 publications

The immune microenvironment and expression of PD‐L1, PD‐1, PRAME and MHC I in salivary duct carcinoma

The immune microenvironment and expression of PD‐L1, PD‐1, PRAME and MHC I in salivary duct carcinoma

A nomogram-based immunoprofile predicts overall survival for previously untreated patients with esophageal squamous cell carcinoma after esophagectomy

PD-L1 Expression in Esophageal Squamous Cell Carcinoma: A Comparative Analysis of 3 Different Antibodies

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