The Head and Neck Squamous Cell Carcinoma Microenvironment as a Potential Target for Cancer Therapy

Plzák, Jan; Bouček, J; Bandúrová, Veronika; Kolář, Michal; Hradilová, Miluše; Szabó, Pavol; Lacina, Lukáš; Chovanec, Martin; Smetana, Karel

doi:10.3390/cancers11040440

Cited by 46 publications

(33 citation statements)

References 135 publications

(141 reference statements)

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“…The most significant biological processes that appear to negatively correlate with the immune risk are IFN-α responses, IFN-γ responses, IL-2/STAT5 signaling and IL-6/JAK/STAT3 signaling, all of which were associated with tumor immunity. IL-6, and IFN-α/γ are prominent mediators of intercellular crosstalk [28]. IFN-γ, a key cytokine that is produced by activated T cells, natural killer (NK) cells and NK T cells, coordinates tumor immune responses [29,30].…”

Section: Discussionmentioning

confidence: 99%

“…These represent potential immunosuppressive targets to expand the therapeutic window of anti-PD-1/ PD-L1 treatment. Modulation of intercellular signaling in the tumor microenvironment could be an efficacious therapeutic modality, and a simultaneous focus on these multiple therapeutic targets may mitigate the risk of a compensatory bypass in a targeted pathway [28].…”

Section: Discussionmentioning

confidence: 99%

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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: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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 conclusion, the immune system plays an important role in the microenvironment of preneoplastic and neoplastic lesion; the knowledge on the role that the microenvironment plays in controlling the local aggressiveness of cancer cells as well as their growth and diffusion have progressively increased over the years and currently it could represent a target for targeted therapies [60]. However, the role played by the microenvironment in the very early stages of the malignant process seems different from the invasive stage.…”

Section: Oral Leukoplakia: Immunopathology and Rationale For The Use mentioning

confidence: 99%

Leukoplakia and Immunology: New Chemoprevention Landscapes?

Grigolato

Bizzoca

Calabrese

et al. 2020

IJMS

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Oral potentially malignant disorders (OPMDs) comprise a range of clinical-pathological alterations frequently characterized by an architectural and cytological derangements upon histological analysis. Among them, oral leukoplakia is the most common type of these disorders. This work aims to analyze the possible use of drugs such as immunochemopreventive agents for OPMDs. Chemoprevention is the use of synthetic or natural compounds for the reversal, suppression, or prevention of a premalignant lesion conversion to malignant form. Experimental and in vivo data offer us the promise of molecular prevention through immunomodulation; however, currently, there is no evidence for the efficacy of these drugs in the chemoprevention action. Alternative ways to deliver drugs, combined use of molecules with complementary antitumor activities, diet influence, and better definition of individual risk factors must also be considered to reduce toxicity, improve compliance to the protocol treatment and offer a better individualized prevention. In addition, we must carefully reconsider the mode of action of many traditional cancer chemoprevention agents on the immune system, such as enhancing immunosurveillance and reversing the immune evasion. Several studies emphasize the concept of green chemoprevention as an alternative approach to accent healthy lifestyle changes in order to decrease the incidence of HNSCC.

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“…SCCs from various organs share some similar features, including their genomic landscapes, morphological characteristics, and molecular alterations [ 2 , 8 ]. Human papillomavirus infection and consumption of alcohol and tobacco are defined etiology factors for SCCs [ 9 ]. To date, SCCs are highly aggressive and current therapeutics have limited effect, and do not provide a satisfactory clinical outcome [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

TP63 links chromatin remodeling and enhancer reprogramming to epidermal differentiation and squamous cell carcinoma development

Man

Tan

Wang

et al. 2020

Cell. Mol. Life Sci.

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Squamous cell carcinoma (SCC) is an aggressive malignancy that can originate from various organs. TP63 is a master regulator that plays an essential role in epidermal differentiation. It is also a lineage-dependent oncogene in SCC. ΔNp63α is the prominent isoform of TP63 expressed in epidermal cells and SCC, and overexpression promotes SCC development through a variety of mechanisms. Recently, ΔNp63α was highlighted to act as an epidermal-specific pioneer factor that binds closed chromatin and enhances chromatin accessibility at epidermal enhancers. ΔNp63α coordinates chromatin-remodeling enzymes to orchestrate the tissue-specific enhancer landscape and three-dimensional high-order architecture of chromatin. Moreover, ΔNp63α establishes squamous-like enhancer landscapes to drive oncogenic target expression during SCC development. Importantly, ΔNp63α acts as an upstream regulator of super enhancers to activate a number of oncogenic transcripts linked to poor prognosis in SCC. Mechanistically, ΔNp63α activates genes transcription through physically interacting with a number of epigenetic modulators to establish enhancers and enhance chromatin accessibility. In contrast, ΔNp63α also represses gene transcription via interacting with repressive epigenetic regulators. ΔNp63α expression is regulated at multiple levels, including transcriptional, post-transcriptional, and post-translational levels. In this review, we summarize recent advances of p63 in epigenomic and transcriptional control, as well as the mechanistic regulation of p63.

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The Head and Neck Squamous Cell Carcinoma Microenvironment as a Potential Target for Cancer Therapy

Cited by 46 publications

References 135 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

Leukoplakia and Immunology: New Chemoprevention Landscapes?

TP63 links chromatin remodeling and enhancer reprogramming to epidermal differentiation and squamous cell carcinoma development

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