scholarly journals The Role of Interleukin-33 in Head and Neck Squamous Cell Carcinoma Is Determined by Its Cellular Sources in the Tumor Microenvironment

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 ◽  
Vol 13 (1) ◽  
Author(s):  
Areeg Elmusrati ◽  
Justin Wang ◽  
Cun-Yu Wang

AbstractHead and neck squamous cell carcinoma (HNSCC), an aggressive malignancy, is characterized by high morbidity and low survival rates with limited therapeutic options outside of regional surgery, conventional cytotoxic chemotherapy, and irradiation. Increasing studies have supported the synergistic role of the tumor microenvironment (TME) in cancer advancement. The immune system, in particular, plays a key role in surveillance against the initiation, development, and progression of HNSCC. The understanding of how neoplastic cells evolve and evade the immune system whether through self-immunogenicity manipulation, or expression of immunosuppressive mediators, provides the foundation for the development of advanced therapies. Furthermore, the crosstalk between cancer cells and the host immune system have a detrimental effect on the TME promoting angiogenesis, proliferation, and metastasis. This review provides a recent insight into the role of the key inflammatory cells infiltrating the TME, with a focus on reviewing immunological principles related to HNSCC, as cancer immunosurveillance and immune escape, including a brief overview of current immunotherapeutic strategies and ongoing clinical trials.


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 ◽  
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.


2019 ◽  
Vol 4 (2) ◽  
pp. 19-26
Author(s):  
Marzieh Norouzian ◽  
Sima Balouchi-Anaraki

For more progress in head and neck squamous cell carcinoma (HNSCC) immuno-oncology, further understanding of interactions between tumor and immune system as well as factors in the tumor microenvironment is required. HNSCC is seriously infiltrated by lymphocytes but is known to be highly immunosuppressive. The aim of this review is to highlight the complexity of tumor microenvironment and tumor- immune cells interaction in the HNSCC, in order to improve understanding of tumorigenesis and disease progression in HNSCC patient and to provide valuable information about prognostic markers. The main goal of this review is to discuss the role of the tumor infiltrating lymphocytes in tumor progression, their cross-talk with other components of the tumor microenvironment as well as their roles in carcinogenesis, metastasis process, treatment, and prognosis in head and neck squamous cell carcinomas.


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