Tumor Clearance and Immune Cell Recruitment in UV‐Induced Murine Squamous Cell Carcinoma Exposed to Ablative Fractional Laser and Imiquimod Treatment

2021 ◽  
Author(s):  
Silvia Fontenete ◽  
Catharina M. Lerche ◽  
Uwe Paasch ◽  
Mirna Perez‐Moreno ◽  
Uffe H. Olesen ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Immune Cell ◽  
Fractional Laser ◽  
Cell Recruitment ◽  
Ablative Fractional Laser ◽  
Tumor Clearance ◽  
Immune Cell Recruitment

scholarly journals Bioinformatics analysis of DNMT1 expression and its role in head and neck squamous cell carcinoma prognosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jili Cui ◽  
Lian Zheng ◽  
Yuanyuan Zhang ◽  
Miaomiao Xue
Keyword(s):  
Gene Expression ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Immune Cell ◽  
Neck Squamous Cell Carcinoma ◽  
Hub Genes ◽  
Significant Difference ◽  
Dnmt1 Expression

AbstractHead and neck squamous cell carcinoma (HNSCC) is the sixth most common type of malignancy in the world. DNA cytosine-5-methyltransferase 1 (DNMT1) play key roles in carcinogenesis and regulation of the immune micro-environment, but the gene expression and the role of DNMT1 in HNSCC is unknown. In this study, we utilized online tools and databases for pan-cancer and HNSCC analysis of DNMT1 expression and its association with clinical cancer characteristics. We also identified genes that positively and negatively correlated with DNMT1 expression and identified eight hub genes based on protein–protein interaction (PPI) network analysis. Enrichment analyses were performed to explore the biological functions related with of DNMT1. The Tumor Immune Estimation Resource (TIMER) database was performed to explore the relationship between DNMT1 expression and immune-cell infiltration. We demonstrated that DNMT1 gene expression was upregulated in HNSCC and associated with poor prognosis. Based on analysis of the eight hub genes, we determined that DNMT1 may be involved in cell cycle, proliferation and metabolic related pathways. We also found that significant difference of B cells infiltration based on TP 53 mutation. These findings suggest that DNMT1 related epigenetic alterations have close relationship with HNSCC progression, and DNMT1 could be a novel diagnostic biomarker and a promising therapeutic target for HNSCC.

scholarly journals Cytokine/chemokine profiles in squamous cell carcinoma correlate with precancerous and cancerous disease stage

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Zewen K. Tuong ◽  
Andrew Lewandowski ◽  
Jennifer A. Bridge ◽  
Jazmina L. G. Cruz ◽  
Miko Yamada ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Proinflammatory Cytokine ◽  
Cytokine Production ◽  
Immune Cell ◽  
Disease Stage ◽  
Proinflammatory Cytokine Production ◽  
Chemokine Production ◽  
Disease Spectrum

AbstractActinic Keratosis (AK), Intraepidermal Carcinoma (IEC), and Squamous Cell Carcinoma (SCC) are generally considered to be advancing stages of the same disease spectrum. However, while AK often regress spontaneously, and IEC often regress in response to immune-activating treatments, SCC typically do not regress. Therefore, it is vital to define whether fundamental immunological changes occur during progression to SCC. Here we show that proinflammatory cytokine expression, chemokine expression, and immune cell infiltration density change during progression to SCC. Our findings suggest a switch from predominantly proinflammatory cytokine production to chemokine production is a key feature of progression from precancer to cancer. Together, these observations propose a model that can underpin current research and open new avenues of exploration into the clinical significance of these profiles with respect to immunotherapeutic or other treatment outcomes.

scholarly journals The Use of Epidermal Growth Factor Receptor Monoclonal Antibodies in Squamous Cell Carcinoma of the Head and Neck

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Jeffery S. Russell ◽  
A. Dimitrios Colevas
Keyword(s):  
Squamous Cell Carcinoma ◽  
Monoclonal Antibodies ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Egf Receptor ◽  
Immune Cell ◽  
Treatment Strategies ◽  
Regular Component ◽  
Specific Patient

Targeting of the EGF receptor (EGFR) has become a standard of care in several tumor types. In squamous cell carcinoma of the head and neck, monoclonal antibodies directed against EGFR have become a regular component of therapy for curative as well as palliative treatment strategies. These agents have anti-tumor efficacy as a single modality and have demonstrated synergistic tumor killing when combined with radiation and/or chemotherapy. While cetuximab has been the primary anti-EGFR monoclonal antibody used in the US, variant anti-EGFR monoclonal antibodies have been used in several clinical studies and shown benefit with improved toxicity profiles. Next generation anti-EGFR monoclonal antibodies may demonstrate multi-target epitope recognition, enhanced immune cell stimulation, or conjugation with radioisotopes in order to improve clinical outcomes. Identification of the specific patient subset that would optimally benefit from anti-EGFR monoclonal antibodies remains an elusive goal.

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 HLA-DR regulates macrophage phenotypic transformation and affects malignant behavior in esophageal squamous cell carcinoma

2020 ◽  
Author(s):  
Jiang Fen Li ◽  
Yu Fang Xie ◽  
Wei Hua Liang ◽  
Hai Jun Zhang ◽  
Xue Li Wang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Immune Cell ◽  
Macrophage Polarization ◽  
Biological Behavior ◽  
Invasion And Metastasis ◽  
Hla Dr ◽  
Low Expression

Abstract Background Tumor-associated macrophages (TAMs) are an important immune cell component of the tumor microenvironment. This study aimed to explore the molecular mechanism of TAMs phenotype transformation and the role in the development of esophageal squamous cell carcinoma (ESCC).Methods Co-culture conditions were employed to determine the phenotypic effects of TAMs on ESCC cell biological behavior. Tumor metastasis related molecules VEGF-C and MMP-9 produced by TAMs was evaluated by qRT-PCR and western blot. Expression of HLA-DR was knocked down in TAMs in vitro to determine the effects on macrophage polarization and the biological behavior of ESCC. We determined whether co-injection with M2 TAMs and macrophages depletion affected tumor growth in vivo tumor challenge model. Associations between HLA-DR, TAM density, and clinical outcomes were evaluated in patients with ESCC.Results TAMs in ESCC samples were found to closely reflect the M2 phenotype of TAMs, and exhibited low expression of HLA-DR. Which was involved in ESCC tumor invasion and metastasis. Low expression of HLA-DR positively correlated with high-density of M2 TAMs, indicating high invasiveness and poor prognosis in patients with ESCC. Downregulation of HLA-DR in TAMs led to additional M2-type TAM polarization and more VEGF-C and MMP-9 secretion, promoted the malignant transformation of ESCC.Conclusions These results demonstrate that downregulation of HLA-DR promote the transformation of M2 TAMs, and participate in the invasion and metastasis of ESCC.

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.

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