Prognostic value of immune‐related genes and immune cell infiltration analysis in the tumor microenvironment of head and neck squamous cell carcinoma

Head & Neck ◽  
2020 ◽  
Vol 43 (1) ◽  
pp. 182-197
Author(s):  
Zizhuo Wang ◽  
Huangbo Yuan ◽  
Jia Huang ◽  
Dianxing Hu ◽  
Xu Qin ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Tumor Microenvironment ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Prognostic Value ◽  
Immune Cell ◽  
Neck Squamous Cell Carcinoma ◽  
Immune Cell Infiltration ◽  
Immune Related Genes

scholarly journals Highly Multiplexed Digital Spatial Profiling of the Tumor Microenvironment of Head and Neck Squamous Cell Carcinoma Patients

2021 ◽  
Vol 10 ◽  
Author(s):  
Arutha Kulasinghe ◽  
Touraj Taheri ◽  
Ken O’Byrne ◽  
Brett G. M. Hughes ◽  
Liz Kenny ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Tumor Microenvironment ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Immune Cell ◽  
Checkpoint Inhibitors ◽  
Neck Squamous Cell Carcinoma ◽  
Protein Markers ◽  
Spatial Profiling

BackgroundImmune checkpoint inhibitors (ICI) have shown durable and long-term benefits in a subset of head and neck squamous cell carcinoma (HNSCC) patients. To identify patient-responders from non-responders, biomarkers are needed which are predictive of outcome to ICI therapy. Cues in the tumor microenvironment (TME) have been informative in understanding the tumor-immune contexture.MethodsIn this preliminary study, the NanoString GeoMx™ Digital Spatial Profiling (DSP) technology was used to determine the immune marker and compartment specific measurements in a cohort of HNSCC tumors from patients receiving ICI therapy.ResultsOur data revealed that markers involved with immune cell infiltration (CD8 T-cells) were not predictive of outcome to ICI therapy. Rather, a number of immune cell types and protein markers (CD4, CD68, CD45, CD44, CD66b) were found to correlate with progressive disease. Cross platform comparison with the Opal Vectra (Perkin Elmer) for a number of markers across similar regions of interest demonstrated concordance for pan-cytokeratin, CD8, and PD-L1.ConclusionThis study, to our knowledge, represents the first digital spatial analysis of HNSCC tumors. A larger cohort of HNSCC will be required to orthogonally validate the findings.

scholarly journals Characterization of the immune cell infiltration landscape in head and neck squamous cell carcinoma to aid immunotherapy

2020 ◽  
Author(s):  
Xinhai Zhang ◽  
Tielou Chen ◽  
Boxin Zhang
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Signaling Pathway ◽  
Squamous Cell ◽  
Immune Cell ◽  
Neck Squamous Cell Carcinoma ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Stromal Component

Abstract Background: The tumor microenvironment chiefly consists of tumor cells, and tumor-infiltrating immune cells admixed with the stromal component. The recent clinical trial has shown that the tumor immune cell infiltration is correlated with the sensitivity to immunotherapy and the prognosis of head and neck squamous cell carcinoma (HNSC). However, to date, the immune infiltrative landscape of HNSC has not yet been elucidated. Methods: We proposed two computational algorithms to unravel the immune infiltration landscape of 1029 HNSC patients. The Boruta algorithm and principal component algorithms (PCA) were employed to quantify three immune cell infiltration gene subtypes categorized as per the immune cell infiltrations pattern. Results: The high ICI score subtype was characterized by a higher tumor mutation burden (TMB) and the immune-activated signaling pathway. However, a low ICI score subtype was categorized as per the activation of immunosuppressive signaling pathways such as TGF-BETA, WNT signaling pathway, and lower TMB. Two immunotherapy cohorts confirmed patients with higher ICI score demonstrated significant therapeutic advantages and clinical benefits.Conclusions: This demonstrated that the ICI score could serve as an effective prognostic biomarker and predictive indicator for immunotherapy. A comprehensive understanding of the HNSC immune landscape might help in tailoring immunotherapeutic strategies for different patients.

scholarly journals Identification of Immune-related lncRNA Panel for Predicting Immune Checkpoint Blockade and Prognosis in Head and Neck Squamous Cell Carcinoma

2021 ◽  
Author(s):  
Chongchang Zhou ◽  
Guowen Zhan ◽  
Zhisen Shen ◽  
Yi Shen ◽  
Hongxia Deng ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Immune Cell ◽  
Risk Model ◽  
Low Risk ◽  
Neck Squamous Cell Carcinoma ◽  
Cell Infiltration ◽  
Immune Cell Infiltration

Abstract Immunotherapy is changing head and neck squamous cell carcinoma (HNSCC) treatment pattern. According to the Chinese Society of Clinical Oncology (CSCO) guidelines, immunotherapy has been deemed as first-line recommendation for recurrent/metastatic HNSCC, marking that advanced HNSCC has officially entered the era of immunotherapy. Long non-coding RNAs impact every step of cancer immunity. Therefore, reliable immune-lncRNA able to accurately predict the immune landscape and survival of HNSCC are crucial to clinical management. In the current study, we downloaded the transcriptomic and clinical data of HNSCC from The Cancer Genome Altas and identified differentially expressed immune-related lncRNAs (DEir-lncRNAs). Further then, Cox and least absolute shrinkage and selection operator (LASSO) regression analyses were performed to identify proper DEir-lncRNAs to construct optimal risk model. Low-risk and high-risk groups were classified based on the optimal cut-off value generated by the areas under curve for receiver operating characteristic curves (AUC), and Kaplan-Meier survival curves were utilized to validate the prediction model. We then evaluated the model based on the clinical factors, immune cell infiltration, chemotherapeutic and immunotherapeutic efficacy between two groups. Our results constructed a risk model consisted of 18 DEir-lncRNA pairs showing significantly association with survival of patients with HNSCC. Besides, HNSCC patients with low risk score significantly enriched of CD8+ T cell, and corelated with high chemosensitivity and immunotherapeutic sensitivity. In summary, our risk model could be served as a promising clinical prediction indicator, effective discoursing of the immune cell infiltration of HNSCC patients, and distinguishing patients who could benefit from chemotherapy and immunotherapy.

scholarly journals Characterization of Molecular Subtypes in Head and Neck Squamous Cell Carcinoma With Distinct Prognosis and Treatment Responsiveness

2021 ◽  
Vol 9 ◽  
Author(s):  
Pei Zhang ◽  
Shue Li ◽  
Tingting Zhang ◽  
Fengzhen Cui ◽  
Ji-Hua Shi ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Immune Cell ◽  
Neck Squamous Cell Carcinoma ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Oncogenic Signaling ◽  
Mtorc1 Signaling

Head and neck squamous cell carcinoma (HNSCC) is one of the most aggressive malignancies with complex phenotypic, etiological, biological, and clinical heterogeneities. Previous studies have proposed different clinically relevant subtypes of HNSCC, but little is known about its corresponding prognosis or suitable treatment strategy. Here, we identified 101 core genes from three prognostic pathways, including mTORC1 signaling, unfold protein response, and UV response UP, in 124 pairs of tumor and matched normal tissues of HNSCC. Moreover, we identified three robust subtypes associated with distinct molecular characteristics and clinical outcomes using consensus clustering based on the gene expression profiles of 944 HNSCC patients from four independent datasets. We then integrated the genomic information of The Cancer Genome Atlas (TCGA) HNSCC cohort to comprehensively evaluate the molecular features of different subtypes and screen for potentially effective therapeutic agents. Cluster 1 had more arrested oncogenic signaling, the highest immune cell infiltration, the highest immunotherapy and chemotherapeutic responsiveness, and the best prognosis. By contrast, Cluster 3 showed more activated oncogenic signaling, the lowest immune cell infiltration, the lowest immunotherapy and chemotherapy responsiveness, and the worst prognosis. Our findings corroborate the molecular diversity of HNSCC tumors and provide a novel classification strategy that may guide for prognosis and treatment allocation.

scholarly journals Immune cell infiltration in head and neck squamous cell carcinoma and patient outcome: a retrospective study

2018 ◽  
Vol 57 (9) ◽  
pp. 1165-1172 ◽  
Author(s):  
Karolin Schneider ◽  
Etienne Marbaix ◽  
Caroline Bouzin ◽  
Marc Hamoir ◽  
Pierre Mahy ◽  
...  
Keyword(s):  
Patient Outcome ◽  
Squamous Cell Carcinoma ◽  
Retrospective Study ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Immune Cell ◽  
Neck Squamous Cell Carcinoma ◽  
Cell Infiltration ◽  
Immune Cell Infiltration

scholarly journals LIM Homeobox Transcription Factors as Novel Prognosis Biomarkers in Head and Neck Squamous Cell Carcinoma

2021 ◽  
Author(s):  
Chen Lu ◽  
Cong-cong Duan ◽  
Han Bing
Keyword(s):  
Squamous Cell Carcinoma ◽  
Transcription Factors ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Immune Cell ◽  
Enrichment Analysis ◽  
Neck Squamous Cell Carcinoma ◽  
Immune Cell Infiltration ◽  
Clinical Variables

Abstract Background: LIM class homeobox (LHX) genes, an important subfamily of the homeobox genes, encode transcription factors that have a fundamental role during embryonic development. However, knowledge regarding the function and mechanism of LHXs in head and neck squamous cell carcinoma (HNSCC) is still lacking. Methods: We conduct a bioinformatic analysis to systematically explore the mRNA expression, clinical correlation, prognostic values, and underlying mechanisms of distinct LHXs in HNSCC. The differentially expressed mRNAs in the LIM homeobox gene family and their correlation with clinical variables were determined and verified with packages in software R. The prognosis values of LHXs expression levels were evaluated by Kaplan-Meier (KM) method and Cox proportional hazard model. Gene set enrichment analysis (GSEA) was conducted to understand the potential biological function of LHXs. The immune cell infiltration patterns were estimated through CIBERSORT and TIMER, and the methylation levels of LHXs in HNSCC were explored in UALCAN and MEXPRESS.Results: We found that among 12 LHXs, 8 genes (ISL1, LHX1-3, 5, 9, LMX1A, and LMX1B) showed altered expression in HNSCC tissues and detected significant correlations between their expression and clinical variables. Survival analysis revealed that LHX1, LHX5, LMX1A, LMX1B can serve as unfavorable prognosis predictors, and ISL1, LHX2, LHX9 can serve as favorable predictors in all HNSCC patients. Gene sets enrichment analysis and immune infiltration analyses showed that the aberrant expression of LHXs was closely related to cancer-associated processes and immune cell infiltration patterns. Finally, we observed hyper-methylation in the promoters of ISL1, LHX2, 5, 9, LMX1A, LMX1B and hypo-methylation in LHX3 promoter, suggesting the regulatory mechanism of LHXs abnormal expression may be related to aberrant DNA methylation. Conclusions: Our study found the oncogenic roles of LHX1,5 and LMX1B and the tumor-suppressor roles of ISL1 and LHX2 in patients with HNSCC, suggesting these LHXs as novel diagnostic and prognostic biomarkers for HNSCC.

scholarly journals Molecular Characteristics, Prognostic Value, and Immune Characteristics of m6A Regulators Identified in Head and Neck Squamous Cell Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiuchao Geng ◽  
Yuhao Zhang ◽  
Zhaomu Zeng ◽  
Zhongrui Zhu ◽  
Hong Wang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Prognostic Value ◽  
Immune Cell ◽  
Molecular Level ◽  
Neck Squamous Cell Carcinoma ◽  
Molecular Characteristics ◽  
Gene Set

N6-methyladenosine (m6A) plays crucial roles in a diverse range of physiological and pathological processes, and it is believed that it tremendously promotes neoplasia and progression. However, knowledge of the molecular characteristics of m6A modification, its prognostic value, and the infiltration of immune cell populations in head and neck squamous cell carcinoma (HNSCC) is still insufficient. Therefore, a pan-cancer genomic analysis was systematically performed here by examining m6A regulators at the molecular level within 33 multiple cancer types, and the correlations between the expression of m6A molecules were researched using datasets from The Cancer Genome Atlas (TCGA). Based on the above analysis, insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) is upregulated in HNSCC and may serve as an independent prognostic factor of overall survival, thus showing potential as a prognostic biomarker in HNSCC. Genetic alteration analyses elucidated the reasons for the abnormal upregulation of IGF2BP2 in HNSCC. As a result, IGF2BP2 was selected for further univariate and multivariate analyses. The functions of the related genes were annotated through gene set enrichment analysis, and the activation states of multiple biological pathways were shown by gene set variation analysis. We found that LRRC59 and STIP1 may act as IGF2BP2-associated genes to have a regulatory function in the m6A modification. In addition, we found that the status of immune cell infiltration was correlated with the level of IGF2BP2 gene expression. Our results provide supplementation at the molecular level for epigenetic regulation in HNSCC and insight into effective immunotherapy targets and strategies.

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