Infiltration of FoxP3+ Regulatory T Cells is a Strong and Independent Prognostic Factor in Head and Neck Squamous Cell Carcinoma

Seminerio, Imelda; Descamps, Géraldine; Dupont, Sophie; Marrez, L. De; Laigle, J.; Lechien, Jérôme R.; Kindt, Nadège; Journé, Fabrice; Saussez, Sven

doi:10.3390/cancers11020227

Cited by 70 publications

(80 citation statements)

References 39 publications

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“…The microenvironment of immunodepression is characterized by the infiltration of immune cells such as Tregs [9]. Strong infiltration of forkhead/winged-helix transcription factor box P3 (FoxP3) + Tregs in HNSCC is associated with improved OS [33,34]. Likewise, our results also demonstrate that Tregs were enriched in low immune risk groups.…”

Section: Discussionsupporting

confidence: 57%

Immune-related gene signature for predicting the prognosis of head and neck squamous cell carcinoma

She

Kong

et al. 2020

Cancer Cell Int

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Background: Immune-related genes (IRGs) were linked to the prognosis of head and neck squamous cell carcinoma (HNSCC). This study aimed to identify the effects of an immune-related gene signature (IRGS) that can predict the of HNSCC prognosis. Methods: The expression data of 770 HNSCC patients from the TCGA database and the GEO database were used. To explore a predictive model, the Cox proportional hazards model was applied. The Kaplan-Meier survival analysis, as well as univariate and multivariate analyses were performed to evaluate the independent predictive value of IRGS. To explore biological functions of IRGS, enrichment analyses and pathway annotation for differentially expressed genes (DEGs) in different immune groups were applied, as well as the immune infiltration. Results: A prognostic signature comprising 27 IRGs was generated. IRGS significantly stratified HNSCC patients into high and low immune risk groups in regard to overall survival in the training cohort (HR = 3.69, 95% CI 2.73-4.98, P < 0.001). Likewise, IRGS could be linked to the prognosis of HNSCC in patients of the validation cohort (HR = 1.84, 95% CI 1.21-2.81, P < 0.01). Even after adjusting for TNM stage, IRGS was maintained as an independent predictor in the multivariate analysis (HR = 3.62, 95% CI 2.58-5.09, P < 0.001), and in the validation cohort (HR = 1.73, 95% CI 1.12-2.67, P = 0.014). The IFN-α response, the IFN-γ response, IL-2/STAT5 signaling, and IL-6/JAK/STAT3 signaling were all negatively correlated with the immune risk (P < 0.01). Immune infiltration of the high-risk group was significantly lower than that of the low-risk group (P < 0.01). Most notably, the infiltration of CD8 T cells, memory-activated CD4 T cells, and regulatory T cells was strongly upregulated in the low immune risk groups, while memory resting CD4 T cell infiltration was downregulated (P < 0.01). Conclusion: Our analysis provides a comprehensive prognosis of the immune microenvironments and outcomes for different individuals. Further studies are needed to evaluate the clinical application of this signature.

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Section: Discussionsupporting

confidence: 57%

Immune-related gene signature for predicting the prognosis of head and neck squamous cell carcinoma

She

Kong

et al. 2020

Cancer Cell Int

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“…In cancer, Tregs contribute to tumor immune escape by suppressing the antitumor response. Some studies had reported that higher Foxp3 + Treg cell infiltration was associated with poorer patient survival in most tumors, but not in HNSCC [48,49]. Our results show that the high level of Tregs infiltration is significantly associated with the low risk score, which is associated with favorable prognosis.…”

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

confidence: 42%

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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“…This disruption induced tumor‐promoting Treg differentiation, and increased anti‐inflammatory cytokine Interleukin 10 (IL‐10) production in HNSCCs 47,48 . On the other hand, a high level of FoxP3 + Treg infiltration in HNSCCs was associated with longer RFS and OS 22,49 . This is probably because the presence of a high level of FoxP3 + Treg in tumors indicates an on‐going robust antitumor immune response, which contributes to inhibition of tumor growth.…”

Section: T Cellsmentioning

confidence: 99%

Tumor immune microenvironment in head and neck cancers

Chen

Krinsky

Woolaver

et al. 2020

Molecular Carcinogenesis

110

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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Infiltration of FoxP3+ Regulatory T Cells is a Strong and Independent Prognostic Factor in Head and Neck Squamous Cell Carcinoma

Cited by 70 publications

References 39 publications

Immune-related gene signature for predicting the prognosis of head and neck squamous cell carcinoma

Immune-related gene signature for predicting the prognosis of head and neck squamous cell carcinoma

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

Tumor immune microenvironment in head and neck cancers

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