New modalities of cancer treatment for NSCLC: focus on immunotherapy

Davies, Marianne

doi:10.2147/cmar.s57550

Cited by 69 publications

(60 citation statements)

References 57 publications

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“…Knockout of glycodelin in NSCLC cell lines led to the differential regulation of immune system-relevant genes that exhibit potential as targets for NSCLC therapeutics (26), for example, PD-L1 (CD274), which was upregulated after silencing of PAEP. Our findings provide evidence that glycodelin detection in human serum might be useful to monitor the response of NSCLC patients to tumor treatment.…”

Section: Discussionmentioning

confidence: 99%

Glycodelin: A New Biomarker with Immunomodulatory Functions in Non–Small Cell Lung Cancer

Schneider

Granzow

Warth

et al. 2015

Clinical Cancer Research

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Purpose: In recent years, immune therapeutic strategies against non–small cell lung cancer (NSCLC) based on tissue-derived biomarkers, for example PD1/PD-L1 (CD274), have evolved as novel and promising treatment options. However, the crosstalk between tumor and immune cells is poorly understood. Glycodelin (gene name PAEP), initially described in the context of pregnancy and trophoblastic implantation, is a secreted immunosuppressive glycoprotein with an as-of-yet largely unknown function in lung cancer. Experimental Design: In this study, we characterized the expression and role of glycodelin in NSCLC through mRNA and protein expression analyses, functional knockdown experiments, and correlations with clinicopathologic parameters. Results: Glycodelin mRNA expression was significantly elevated in tumors (n = 336) compared with matched normal tissue (P < 0.0001). Overall survival (OS) was significantly reduced in NSCLC with high glycodelin mRNA levels in women but not in men. Glycodelin was detected in the sera of patients, and the levels correlated with recurrence and metastatic disease. Knockdown of glycodelin with siRNAs in NSCLC cell lines resulted in significant upregulation of immune system modulatory factors such as PDL1, CXCL5, CXCL16, MICA/B, and CD83 as well as proliferation stimulators EDN1 and HBEGF. Furthermore, decreased migration of tumor cells was observed. Conclusions: Altogether, the comprehensive characterization of glycodelin in NSCLC provides strong support for its use as a biomarker with immune modulatory function. Clin Cancer Res; 21(15); 3529–40. ©2015 AACR.

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Section: Discussionmentioning

confidence: 99%

Glycodelin: A New Biomarker with Immunomodulatory Functions in Non–Small Cell Lung Cancer

Schneider

Granzow

Warth

et al. 2015

Clinical Cancer Research

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“…Given that PTEN was a crucial target of miR-21 in the metastasis of lung cancer cells [28,29], we detected the expression of PTEN in primary human lung cancer cells in response to DPI treatment. DPI treatment resulted in increased mRNA and protein PTEN expressions in primary human lung cancer cells ( Fig.…”

Section: Nox Inhibition Led To Increased Pten Expression and Decreasementioning

confidence: 99%

Inhibition of NADPH oxidase protects against metastasis of human lung cancer by decreasing microRNA-21

et al. 2015

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The objective of this study was to detect the effect of NADPH oxidase (NOX) inhibition on metastasis of lung cancer. Primary human lung cancer cells were isolated from surgical tissues using the Cancer Cell Isolation Kit. Invasion was detected using the BD Biocoat Matrigel Invasion Chamber assay. Expressions of microRNA-21 (miR-21), PTEN, MMP9, and p47 were detected by qPCR. Groups of nude mice were challenged with A549 cells with or without DPI and detected for tumor metastasis and survival. NOX inhibition in human lung cancer cells significantly reduced their invasive potential in vitro. NOX inhibition in vivo led to decreased metastasis of human lung cancer and prolonged the survival time of tumor-bearing nude mice. Further, NOX inhibition resulted in decreased expression of miR-21 in human lung cancer cells. Increased expression of miR-21 abrogated the effect of NOX inhibitor on metastasis of human lung cancer in vitro and in vivo. Decreased expression of miR-21 facilitated the effect of NOX inhibitor on metastasis of human lung cancer in vitro and in vivo. Furthermore, increased expression of PTEN and decreased expression of MMP9 were observed in human lung cancer cells in response to NOX inhibition. Finally, close correlations of miR-21 expression levels with NADPH oxidase expression level and differentiation state of tumor cells were observed in lung cancer patients. Inhibition of NADPH oxidase protected against metastasis of human lung cancer cells by decreasing miR-21 expression, which could facilitate the understanding of lung cancer pathogenesis and provided clues for the development of novel therapeutics for lung cancer patients.

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“…The cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed cell death protein-1 (PD-1) pathways are two of several immune checkpoint pathways that play critical roles in controlling T-cell immune responses [19]. CTLA-4 and PD-1 are expressed by T cells.…”

Section: Future Therapies For Advanced Gcmentioning

confidence: 99%

Gastric Cancer—Epidemiologic and Clinical Aspects

Venerito

Nardone²,

Selgrad

et al. 2014

Helicobacter

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Gastric cancer (GC) continues to be an important health threat as the third leading cause of cancer related death in both sexes worldwide. In a recent analysis, the mortality trends for the time period from 1980 till 2011 were significantly downward in all countries, but the declines in the USA, EU and several other major countries were of low magnitude when compared with the past. Furthermore, the relative contribution of cardia cancers compared with noncardia cancers increased among countries with higher GC rates. With respect to preneoplastic changes of the gastric mucosa, a large population-based study suggests that Helicobacter pylori infection and antigastric parietal cell antibodies-mediated autoimmune response might, for the most part, be independent and follow distinct pathways rather than causally related pathways leading to chronic atrophic gastritis. A large prospective, randomized, open-label Korean trial questioned the role of H. pylori eradication for the prevention of metachronous lesions after endoscopic resection of early GC. A review of 1258 Japanese cases undergoing curative endoscopic submucosa dissection for early GC showed that scheduled follow-up endoscopy is mandatory for detecting metachronous lesions at an early stage, where they can be treated by endoscopic resection. Ramucirumab, a vascular endothelial growth factor receptor-2 antagonist, is the first biological treatment that provides survival benefits to patients with advanced GC in progress after first-line chemotherapy. The target agent rilotumumab is currently being evaluated in patients with advanced GC overexpressing the HGF/c-MET signaling pathway. In the near future, ipilimumab and nivolumab, two immunostimulatory monoclonal antibodies with antineoplastic effects, might offer new therapeutic options for patients with advanced GC.In 2014, Helicobacter pylori infection is still one of the world's most prevalent infections and continues to represent the major risk factor for gastric cancer (GC), which accounts annually for at least 738,000 deaths Gastric Cancer: Epidemiologic Aspects GC remains the third leading cause of death from cancer worldwide, following lung and liver cancer [2]. A declining incidence of GC has been registered over the past sixty years. However, recent epidemiologic data show that the incidence of noncardia GC in younger age groups (<50 years) remains constant or is even on the rise again in the United States since 1977, whereas

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New modalities of cancer treatment for NSCLC: focus on immunotherapy

Cited by 69 publications

References 57 publications

Glycodelin: A New Biomarker with Immunomodulatory Functions in Non–Small Cell Lung Cancer

Glycodelin: A New Biomarker with Immunomodulatory Functions in Non–Small Cell Lung Cancer

Inhibition of NADPH oxidase protects against metastasis of human lung cancer by decreasing microRNA-21

Gastric Cancer—Epidemiologic and Clinical Aspects

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