<scp>PD</scp>‐1 and <scp>PD</scp>‐L1 expression in <scp>HNSCC</scp> primary cancer and related lymph node metastasis – impact on clinical outcome

Schneider, Sven; Kadletz, Lorenz; Wiebringhaus, Robert; Kenner, Lukas; Selzer, Edgar; Füreder, Thorsten; Rajky, Orsolya; Berghoff, Anna Sophie; Heiduschka, Gregor

doi:10.1111/his.13646

Cited by 78 publications

(76 citation statements)

References 31 publications

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“…PD‐1 is also considered a marker for exhausted T cells and is often upregulated in CD4 + and CD8 + TILs in various types of cancers 30,31 . CD8 + TILs of human HNSCCs were found to express increased levels of PD‐1 on their surface, 32 and 66% to 79% of patients with SCC had PD‐L1‐positive tumor cells 33–36 . In addition, we previously showed that CD8 + TILs in a mouse SCC model highly expressed PD‐1 and LAG‐3 37 .…”

Section: T Cellsmentioning

confidence: 99%

Tumor immune microenvironment in head and neck cancers

Chen

Krinsky

Woolaver

et al. 2020

Molecular Carcinogenesis

123

114

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Head and neck cancers are a heterogeneous group of tumors that are highly aggressive and collectively represent the sixth most common cancer worldwide.Ninety percent of head and neck cancers are squamous cell carcinomas (HNSCCs).The tumor microenvironment (TME) of HNSCCs consists of many different subsets of cells that infiltrate the tumors and interact with the tumor cells or with each other through various networks. Both innate and adaptive immune cells play a crucial role in mediating immune surveillance and controlling tumor growth. Here, we discuss the different subsets of immune cells and how they contribute to an immunosuppressive TME of HNSCCs. We also briefly summarize recent advances in immunotherapeutic approaches for HNSCC treatment. A better understanding of the multiple factors that play pivotal roles in HNSCC tumorigenesis and tumor progression may help define novel targets to develop more effective immunotherapies for patients with HNSCC.

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Section: T Cellsmentioning

confidence: 99%

Tumor immune microenvironment in head and neck cancers

Chen

Krinsky

Woolaver

et al. 2020

Molecular Carcinogenesis

123

114

View full text Add to dashboard Cite

show abstract

“…This variance in expression may be due to different sample populations, different preparation methods and the lack of a standardized scoring method for determining positivity. These studies have related PD‐L1 expression levels to clinical–pathological features of the patient and disease (Ahn et al, ; Cho, Yoon, Il, Hong, & Hong, ; Hanna et al, ; Hirai et al, ; Kogashiwa et al, ; Lin et al, ; Maruse et al, ; Oliveira‐Costa et al, ; Satgunaseelan et al, ; Schneider et al, ; Stasikowska‐Kanicka, Wągrowska‐Danilewicz, & Danilewicz, ; Straub et al, ; Troeltzsch et al, ).…”

Section: Clinical Implications Of Pd‐l1 Expression In Osccmentioning

confidence: 99%

An update of knowledge on PD‐L1 in head and neck cancers: Physiologic, prognostic and therapeutic perspectives

et al. 2019

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Programmed cell death‐ligand 1 (PD‐L1) is a transmembrane protein that acts as a co‐inhibitory factor in the immune response. Its receptor, programmed cell death protein 1 (PD‐1), is found on immune cells, where binding to PD‐L1 can reduce the proliferation of PD‐1‐positive cells, inhibit their cytokine secretion and induce apoptosis. PD‐L1 in immune‐privileged tissue plays a crucial role in peripheral tolerance. PD‐L1 can be overexpressed in various malignancies, including oral squamous cell carcinoma, where it can attenuate the host immune response to tumour cells and has been associated with a worse prognosis. Monoclonal antibody therapies targeting the PD‐1:PD‐L1 axis have shown initial promise, but further research is needed to identify which patients will benefit. We provide an update of knowledge on PD‐L1, including its structure, function and regulation. We also review studies on the overexpression of PD‐L1 in cancer, specifically oral squamous cell carcinoma, and explore its potential value as a therapeutic target.

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“…This may be caused by the upregulation of Tregs in HNSCC, suggesting that CTLA-4 may be involved in some aspect of the antitumor effect. Studies have reported that HNSCC patients exhibiting high PD-L1/PD-1 expression tend to have prolonged survival outcomes and a lower probability of recurrence [52,53]. In addition, our signature was negatively correlated with PD-1, but not PD-L1.…”

Section: Genetic Alterations and Gsea Analysis In The High-risk Groupsmentioning

confidence: 60%

A novel comprehensive immune-related gene signature as a promising survival predictor for head and neck squamous cell carcinoma

Fang

Chen

Liao

et al. 2020

Preprint

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Background: Head and neck squamous cell carcinoma (HNSCC), the most frequent subtype of head and neck cancer, continues to have a poor prognosis with no improvement. Growing evidence has demonstrated that the immune system plays a crucial role in the development and progression of HNSCC. The goal of our study was to develop an immune-related signature for accurately predicting the survival of HNSCC patients. Methods: Gene expression profiles were established from a total of 546 HNSCC and normal tissues to establish a training set and 83 HNSCC tissues for a validation set. Differentially expressed prognostic immune genes were identified by univariate Cox regression analysis and a corresponding network of differentially expressed transcription factors (TFs) were identified using Cytoscape. The immune-related gene signature was established and validated by univariate Cox regression analysis, least absolute shrinkage and selector operation (LASSO), and multivariate Cox regression analyses. In addition, the prognostic value of the immune-related signature was analyzed by survival and Cox regression analysis. Finally, the correlation between the immune-related signature and the immune microenvironment was established.Results: In this study, the TF-mediated network revealed that Foxp3 plays a central role in the regulatory mechanism of most immune genes. A prognostic signature based on 10 immune-related genes, which divided patients into high and low risk groups, was developed and successfully validated using two independent databases. Our prognostic signature was significantly related to worse survival and predicted prognosis in patients with different clinicopathological factors. A nomogram including clinical characteristics was also constructed for accurate prediction. Furthermore, it was determined that our prognostic signature may act as an independent factor for predicting the survival of HNSCC patients. ROC analysis also revealed that our signature had superior predictive value compared with TNM stage. As for the immune microenvironment, our signature showed a positive correlation with activated mast cells and M0 macrophages, a negative correlation with Tregs, and immune checkpoint molecules PD-1 and CLTA-4. Conclusions: Our study established an immune-related gene signature, which not only provides a promising biomarker for survival prediction, but may be evaluated as an indicator for personalized immunotherapy in patients with HNSCC.

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PD‐1 and PD‐L1 expression in HNSCC primary cancer and related lymph node metastasis – impact on clinical outcome

Abstract: Our results characterise the expression profiles of PD-1 axis proteins in HNSCC which might serve as possible clinical prognostic markers.

Cited by 78 publications

References 31 publications

Tumor immune microenvironment in head and neck cancers

Tumor immune microenvironment in head and neck cancers

An update of knowledge on PD‐L1 in head and neck cancers: Physiologic, prognostic and therapeutic perspectives

A novel comprehensive immune-related gene signature as a promising survival predictor for head and neck squamous cell carcinoma

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