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 Identification of factors related to immunotherapy efficacy and prognosis in patients with advanced head and neck squamous cell carcinoma

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Xuanli Xu ◽  
Rongrong Li ◽  
Lin Zhang ◽  
Guopei Zhu ◽  
Dandan Ren ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Immune Cell ◽  
Gene Mutations ◽  
Neck Squamous Cell Carcinoma ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Mutation Burden

Abstract Background Immunotherapy is an important treatment in oncology, but only a fraction of patients with head and neck squamous cell carcinoma (HNSCC) benefit from it. Therefore, the aim of this study was to identify predictive biomarkers of immunotherapy response for HNSCC in order to improve treatment outcomes. Methods Survival analyses and comparative efficacy evaluation were performed to investigate prognostic and therapeutic impact factors in patients with advanced HNSCC following immunotherapy, and to examine the effects of factors including gene mutations, tumor mutational burden (TMB), mutant-allele tumor heterogeneity (MATH), and immune cell infiltration on the survival and efficacy. Results Anti-PD-1 treatment led to a prolonged overall survival (OS) in HNSCC patients with gene mutations compared with those without the mutations, while no significant difference in the OS was found between the two groups of patients. And no marked association between the MATH value and OS was detected in HNSCC patients, whereas patients with either high TMB scores in tissues and blood or high immune cell infiltration displayed a significantly longer OS. Further analysis with efficacy as the primary endpoint revealed no significant differences in the tissue TMB, blood TMB, and MATH value between the patients who responded to immunotherapy and those who did not. Moreover, no significant differences in the expression percentages of positive immune cells in tumor, stroma, and total regions were identified between the above two groups of patients. Conclusion HNSCC is characterized by high mutation rate, high mutation burden, and high level of immune cell infiltration, and a subset of HNSCC patients respond to immunotherapy. Here, we showed that high mutation burden and immune cell infiltration may improve the prognosis of HNSCC patients with immunotherapy, while there was no remarkable effect on the efficacy.

scholarly journals FOXD1 is a prognostic biomarker and correlated with macrophages infiltration in head and neck squamous cell carcinoma

2021 ◽  
Author(s):  
Huazhen Liang ◽  
Chunning Zhang ◽  
Chaoming Li ◽  
Changguo Li ◽  
Yanli Wang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Immune Cell ◽  
Neck Squamous Cell Carcinoma ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Clinical Prognosis ◽  
Cancer Data

Background: FOXD1 (Forkhead Box D1) is differentially expressed in various tumors. However, its role and correlation with immune cell infiltration remains uncertain in head and neck squamous cell carcinoma (HNSC). Methods: FOXD1 expression was analyzed in TCGA (The Cancer Genome Atlas) pan-cancer data. The clinical prognosis influence of FOXD1 was evaluated by clinical survival data of TCGA. Enrichment analysis of FOXD1 was performed using R packages “clusterProfiler”. We downloaded the immune cell infiltration score of TCGA samples from published articles, and analyzed the correlation between immune cell infiltration level and FOXD1 expression. Results: FOXD1 was highly expressed and associated with poorer overall survival (OS p<0.0001), disease-specific survival (DSS p=0.00011) and progression-free interval (PFI p<0.0001) in HNSC and some other tumors. In addition, FOXD1 expression was significantly correlated with infiltration of immune cells. Tumor associated macrophages (TAM) infiltration increased in tissues with high FOXD1 expression in HNSC. Immunosuppressive genes such as PD-L1, IL-10, TGFB1, and TGFBR1 were significantly positively correlated with FOXD1. Conclusions: Our study suggests FOXD1 to be an oncogene and act as an indicator of poor prognosis in HNSC. FOXD1 might contribute to the TAM infiltration in HNSC. High FOXD1 may be associated with tumor immunosuppression status.

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