scholarly journals Low-dose IFN-γ induces tumor cell stemness in tumor microenvironment of non-small cell lung cancer

2019 ◽  
Author(s):  
Mengjia Song ◽  
Yu Ping ◽  
Kai Zhang ◽  
Li Yang ◽  
Feng Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Low Dose ◽  
Small Cell ◽  
Small Cell Lung ◽  
Low Level ◽  
Ifn Γ ◽  
Dose Dependent

AbstractInterferon-γ (IFN-γ) is conventionally recognized as an inflammatory cytokine that play a central role in antitumor immunity. Clinically, although has been used clinically to treat a variety of malignancies, low-level IFN-γ in the tumor microenvironment (TME) increases the risk of tumor metastasis during immunotherapy. Accumulating evidence has suggested that IFN-γ can induce cancer progression. The mechanisms underlying the controversial role of IFN-γ regulating tumor development remain unclear. Herein, we firstly revealed a dose-dependent effect of IFN-γ in inducing tumor stemness to accelerate cancer progression in patients with a variety of cancer types. Mechanically, low-level IFN-γ endowed cancer stem-like properties via the intercellular adhesion molecule-1 (ICAM1)-PI3K-Akt-Notch1 axis, whereas high-level IFN-γ activated the JAK1-STAT1-caspase pathway to induce apoptosis in non-small cell lung cancer (NSCLC). Inhibition of ICAM1 abrogated the stem-like properties of NSCLC cells induced by the low dose of IFN-γ both in vitro and in vivo. Our study first defines the role of low-level IFN-γ in conferring tumor stemness and clearly elucidate the distinct signaling pathways activated by IFN-γ in a dose-dependent manner, providing new insights into cancer treatment, particularly patients with low-level IFN-γ expression in the TME.

Abstract 4450: The role of paired-like homeodomain 2B in non-small cell lung cancer progression

2017 ◽  
Author(s):  
Sheng-Yi Lin ◽  
Yu-Han Huang ◽  
Yi-Hua Lai ◽  
Sung-Liang Yu ◽  
Sheng-Fang Su ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Progression ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung

scholarly journals Role of SOX Protein Groups F and H in Lung Cancer Progression

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3235
Author(s):  
Mateusz Olbromski ◽  
Marzenna Podhorska-Okołów ◽  
Piotr Dzięgiel
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Progression ◽  
Cell Lung Cancer ◽  
Transcript Level ◽  
Small Cell ◽  
Gene Transcript ◽  
Small Cell Lung ◽  
Lung Cancers

The SOX family proteins are proved to play a crucial role in the development of the lymphatic ducts and the cardiovascular system. Moreover, an increased expression level of the SOX18 protein has been found in many malignances, such as melanoma, stomach, pancreatic breast and lung cancers. Another SOX family protein, the SOX30 transcription factor, is responsible for the development of male germ cells. Additionally, recent studies have shown its proapoptotic character in non-small cell lung cancer cells. Our preliminary studies showed a disparity in the amount of mRNA of the SOX18 gene relative to the amount of protein. This is why our attention has been focused on microRNA (miRNA) molecules, which could regulate the SOX18 gene transcript level. Recent data point to the fact that, in practically all types of cancer, hundreds of genes exhibit an abnormal methylation, covering around 5–10% of the thousands of CpG islands present in the promoter sequences, which in normal cells should not be methylated from the moment the embryo finishes its development. It has been demonstrated that in non-small-cell lung cancer (NSCLC) cases there is a large heterogeneity of the methylation process. The role of the SOX18 and SOX30 expression in non-small-cell lung cancers (NSCLCs) is not yet fully understood. However, if we take into account previous reports, these proteins may be important factors in the development and progression of these malignancies.

The role of LGR5 and ALDH1A1 in non-small cell lung cancer: Cancer progression and prognosis

2015 ◽  
Vol 462 (2) ◽  
pp. 91-98 ◽  
Author(s):  
Fei Gao ◽  
Bin Zhou ◽  
Jun-Chi Xu ◽  
Xin Gao ◽  
Shu-Xiang Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Progression ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung

scholarly journals Low-Dose IFNγ Induces Tumor Cell Stemness in Tumor Microenvironment of Non–Small Cell Lung Cancer

2019 ◽  
Vol 79 (14) ◽  
pp. 3737-3748 ◽  
Author(s):  
Mengjia Song ◽  
Yu Ping ◽  
Kai Zhang ◽  
Li Yang ◽  
Feng Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Microenvironment ◽  
Tumor Cell ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Low Dose ◽  
Small Cell ◽  
Small Cell Lung

scholarly journals Relationship between the invasion of lymphocytes and cytokines in the tumor microenvironment and the interval after single brachytherapy hypofractionated radiotherapy and conventional fractionation radiotherapy in non-small cell lung Cancer

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Lin Li ◽  
Hong Cheng Yue ◽  
Yun Wei Han ◽  
Wei Liu ◽  
Liang Geng Xiong ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Microenvironment ◽  
Tumor Necrosis ◽  
Tumor Volume ◽  
Small Cell ◽  
Small Cell Lung ◽  
Ki 67 ◽  
Expression Levels ◽  
Conventional Fractionation ◽  
Ifn Γ

Abstract Background The effect of brachytherapy on lymphocytes and cytokines in the tumor microenvironment is unclear. This study aimed to analyze the relationship between the invasion of lymphocytes and cytokines in the tumor microenvironment and the interval after single brachytherapy hypofractionated radiotherapy (SBHFRT) and conventional fractionation radiotherapy (CFRT) in non-small cell lung cancer (NSCLC). Methods Lewis tumor-bearing mice were randomly divided into control, CFRT, and SBHFRT groups. On days 7 and 14 after radiation, the expression levels of CD86+, CD4+, CD8+, and Foxp3+ cells, and levels of Ki-67+ protein were detected by immunohistochemistry, and the tumor necrosis rate was calculated. Following this, the levels of interleukin-10 (IL-10), IL-12, and interferon-γ (IFN-γ) were detected by enzyme-linked immunosorbent assay. The apoptosis rate was evaluated via flow cytometry. The tumor volume and tumor growth inhibition rate (TGIR) were calculated on day 14. Tumor metabolism was assessed via 18F-FDG micropositron emission tomography/computer tomography. Results The tumor volume reduced by 22.0% and TGIR increased by 92.2% (p < 0.05) in the SBHFRT group. Further, on days 7 and 14 after radiation, tumor metabolism, Ki-67+ and Foxp3+ expression levels, and IL-10 levels were lower, and tumor necrosis and apoptosis rates; CD86+, CD4+, and CD8+ expression levels; and IL-12 and IFN-γ levels were higher in the SBHFRT group than in the CFRT group, particularly on day 7. Conclusion SBHFRT could lead to more accumulation of dendritic cells, anti-tumor lymphocytes, and cytokines, and further reduce the aggregation of immunosuppressive lymphocytes and cytokines in the tumor microenvironment compared with CFRT, and the difference was the most obvious on day 7 after radiation. The clinical significance of the findings remains to be further verified.

Comprehensive Bioinformatics Analysis Identifies Tumor Microenvironment and Immune-related Genes in Small Cell Lung Cancer

2020 ◽  
Vol 23 (5) ◽  
pp. 381-391 ◽  
Author(s):  
Yongchun Song ◽  
Yanqin Sun ◽  
Tuanhe Sun ◽  
Ruixiang Tang
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
T Cells ◽  
Tumor Microenvironment ◽  
Immune Cells ◽  
Molecular Subtypes ◽  
Small Cell ◽  
Small Cell Lung ◽  
Immune Genes

Background: Tumor microenvironment (TME) cells play important roles in tumor progression. Accumulating evidence show that they can be exploited to predict the clinical outcomes and therapeutic responses of tumor. However, the role of immune genes of TME in small cell lung cancer (SCLC) is currently unknown. Objective: To determine the role of immune genes in SCLC. Methods: We downloaded the expression profile and clinical follow-up data of SCLC patients from Gene Expression Omnibus (GEO), and TME infiltration profile data of 158 patients using CIBERSORT. The correlation between TME phenotypes, genomic features, and clinicopathological features of SCLC was examined. A gene signature was constructed based on TME genes to further evaluate the relationship between molecular subtypes of SCLC with the prognosis and clinical features. Results: We identified a group of genes that are highly associated with TME. Several immune cells in TME cells were significantly correlated with SCLC prognosis (p<0.0001). These immune cells displayed diverse immune patterns. Three molecular subtypes of SCLC (TMEC1-3) were identified on the basis of enrichment of immune cell components, and these subtypes showed dissimilar prognosis profiles (p=0.03). The subtype with the best prognosis, TMEC3, was enriched with immune activation factors such as oncogene M0, oncogene M2, T cells follicular helper, and T cells CD8 (p<0.001). The TMEC1 subtype with the worst prognosis was enriched with T cells CD4 naive, B cells memory and Dendritic cells activated cells (p<0.001). Further analysis showed that the TME was significantly enriched with immune checkpoint genes, immune genes, and immune pathway genes (p<0.01). From the gene expression data, we identified four TME-related genes, GZMB, HAVCR2, PRF1 and TBX2, which were significantly associated with poor prognosis in both the training set and the validation set (p<0.05). These genes may serve as markers for monitoring tumor responses to immune checkpoint inhibitors. Conclusion: This study shows that TME features may serve as markers for evaluating response of SCLC cells to immunotherapy.

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