PD-L1 in combination with CD8+TIL and HIF-1α are promising prognosis predictors of head and neck squamous cell carcinoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e18545-e18545
Author(s):  
Jinming Yu ◽  
Zihan Zhou ◽  
Dianbin Mu ◽  
Dexian Zhang ◽  
Xianbin Zhang ◽  
...  

e18545 Background: Currently, the tumor/node/metastasis (TNM) staging is the most widely used Head and neck squamous cell carcinoma (HNSCC) staging system. However, this classification only provides limit information for the prognosis of HNSCC. Recently, some studies suggest that the level of PD-L1 in tumor cells (TC-PD-L1) or in tumor microenvironment cells (TMC-PD-L1) is a promising biomarker for the prognosis of HNSCC patients. Therefore, in this study, we evaluated the prognostic value of TC-PD-L1, TMC-PD-L1, CD8+ TIL, HIF-1α. In addition, we investigated if incorporated these biomarkers into TNM stage could improve the prognostic value of TNM stage. Methods: A total of 63 patients who underwent surgical resection. The level of PD-L1, CD8+ TIL and HIF-1α was determined by immunohistochemical analysis. The survival of patients was evaluated by Kaplan-Meier analysis and Cox proportional hazards model. The prognostic power of these parameters was evaluated by C-index. Results: We observed that the survival of patients, who had high level of PD-L1 in tumor cells, was significantly shorter than those who had low level of PD-L1. However, the survival of patients who had high level of PD-L1 in tumor microenvironment was significantly longer than patients with low level of PD-L1 in tumor microenvironment. In addition, high level of CD8+ tumor-infiltrating lymphocyte or low level of HIF-1α level suggests a better prognosis. Moreover, we observed that PD-L1 in combination with CD8+tumor-infiltrating lymphocyte and HIF-1α could significantly improve the prognostic effect of current TNM stage. Conclusions: The results of this study suggest that the level of PD-L1, CD8+TIL and HIF-1α is useful prognostic biomarkers for patients with HNSCC. Incorporated these biomarkers into current TNM stage of HNSCC improve the discriminatory capability of TNM stage.

2021 ◽  
Vol 10 ◽  
Author(s):  
Liang Peng ◽  
Wei Sun ◽  
Lin Chen ◽  
Wei-Ping Wen

ObjectivesTo investigate the role of interleukin-33 (IL-33) in head and neck squamous cell carcinoma (HNSCC).Materials and MethodsRNA-seq data of 520 cases of HNSCC were retrieved from The Cancer Genome Atlas. The tumor microenvironment was deconstructed by xCell using bulk RNA-seq data. The cohort was dichotomized by the median IL-33 expression level. Immune cell components and molecular markers were compared between the high and low IL-33 groups. The prognostic value of IL-33 was evaluated by the log-rank test. Differential gene expression analysis and KEGG pathway enrichment analysis were also conducted. The relationship between the IL-33 expression level and the abundance of its potential cellular sources was evaluated by Pearson’s partial correlation test. Subgroup analysis was conducted in laryngeal, oropharyngeal, and oral cavity squamous cell carcinoma (LSCC, OPSCC, and OCSCC).ResultsThe role of IL-33 in HNSCC was heterogeneous among tumors at different sites. In LSCC, IL-33 may increase the extent of malignancy of tumor cells and act as a pro-tumor factor. In OCSCC, IL-33 may play a role in orchestrating the immune responses against tumor cells and act as an antitumor factor. The role of IL-33 in OPSCC was undetermined. IL-33 in LSCC was mainly derived from endothelial cells, while IL-33 in OCSCC was mainly derived from endothelial and epithelial cells.ConclusionAccording to the different sources of IL-33 in LSCC and OCSCC, we propose a hypothesis that stroma-derived IL-33 could favor tumor progression, while epithelial-derived IL-33 could favor antitumor immune responses in HNSCC.


2021 ◽  
Author(s):  
Zhi-Jie Liu ◽  
Li-Sheng Li-Sheng ◽  
Jing Wang ◽  
Li-Xia Peng ◽  
Yan Mei ◽  
...  

Abstract BackgroundAccumulating evidence has shown that dysregulated expression of microRNAs plays a key role in tumorigenesis. To explore the mechanisms of this we conducted this study.MethodsFive Gene Expression Omnibus datasets (GEO) datasets , GSE32960, GSE36682, GSE43039, GSE70970 and GSE118613 and head and neck squamous cell carcinoma data of The Cancer Genome Atlas (TCGA) were analysis in this study.ResultsBy analyzing the microRNA expression profile of nasopharyngeal carcinoma (NPC) in the five GEO datasets, we identified miR-150-5p as potential biomarker for patient survival. To explore the mechanisms of this, We examined the head and neck squamous cell carcinoma data of TCGA and found that miR-150-5p was correlated with high enrichment of tumor-infiltrating B cells, low enrichment of cancer-associated fibroblasts and down-regulated oncogenic pathways. miR-150-5p may also improve the immune response in the tumor microenvironment. These findings may explain how miR-150-5p improves outcome of head and neck squamous cell carcinoma patients including NPC. Additionally, the exosomal long non-coding RNA AC073130.1 was identified as a potential regulator of miR-150-5p. As miR-150-5p can also be released via exosomes, this study provides insight into the cross-talk of tumor cells and B cells in the tumor microenvironment via exosomal AC073130.1 and miR-150-5p. ConclusionMiR-150-5p improves outcome of head and neck squamous cell carcinoma patients by improving the immune response. There might be a cross-talk of tumor cells and B cells in the tumor microenvironment via exosomal AC073130.1 and miR-150-5p.


Author(s):  
Zi-Yi Feng ◽  
Hao-Yu Gao ◽  
Tian-Da Feng

Background: The purpose of this study was to determine the association between m6A-modified lncRNAs, immune infiltration, and PD-L1 expression in patients with primary head and neck squamous cell carcinoma (HNSCC) and the prognostic value of m6A RNA methylation-related lncRNAs in HNSCC.Methods: We downloaded the RNA-seq transcriptome data and the clinical information for HNSCC from the TCGA databases and used consensus clustering analysis to divide the samples into two groups. To identify a risk signature, least absolute shrinkage and selection operator (LASSO) analyses were conducted. the association between m6A-modified lncRNAs, immune infiltration, and PD-L1 expression were detected by using the R packages. What is more, we used cBioPortal tools to identify genomic alterations and PD-L1 mutations and Gene set enrichment analysis (GSEA) was utilized to predict downstream access of two clusters.Results: Notably, lncRNAs play significant roles in tumorigenesis and development. In total, we identified two subtypes of HNSCC according to consensus clustering of the m6A RNA methylation-related lncRNAs, and the T, grade and age were proven to be related to the subtypes. The Cox regression and LASSO analyses identified a risk signature including GRHL3-AS1, AL121845.4, AC116914.2, AL513190.1. The prognostic value of the risk signature was then proven. The selected gene PD-L1 mutations and the immune infiltration in both groups were further explored.Conclusion: Collectively, our study elucidated the important role of m6A RNA methylation- related lncRNAs in tumor microenvironment of HNSCC. The proposed m6A RNA methylation- related lncRNAs might serve as crucial mediators of tumor microenvironment of HNSCC, representing promising therapeutic targets in improving immunotherapeutic efficacy.


2008 ◽  
Vol 23 (1) ◽  
pp. 25-33 ◽  
Author(s):  
David Loose ◽  
Alberto Signore ◽  
Elena Bonanno ◽  
Hubert Vermeersch ◽  
Rudi Dierckx ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document