Dataset Information

Interleukin-10-regulated tumour tolerance in non-small cell lung cancer.

ABSTRACT:

Background

Lung cancer is the most life-threatening cancer type worldwide. Treatment options include surgery, radio- and chemotherapy, as well as the use of immunomodulatory antibodies. Interleukin (IL)-10 is an immunosuppressive cytokine involved in tumour immune escape.

Methods

Immunohistochemistry (IHC) on human lung surgery tissue as well as human tumour cell line cultures, FACS analysis, real-time PCR and experimental lung cancer.

Results

Here we discovered a positive correlation between IL-10 and IL-10 receptor (IL-10R) expression in the lung with tumour diameter in patients with lung cancer (non-small cell lung cancer), the most life-threatening cancer type worldwide. IL-10 and IL-10R were found induced in cells surrounding the lung tumour cells, and IL-10R was mainly expressed on the surface of Foxp-3⁺ T-regulatory lymphocytes infiltrating the tumour of these patients where its expression inversely correlated with programmed cell death 1. These findings were confirmed in translational studies. In a human lung adenocarcinoma cell line, IL-10R was found induced under metabolic restrictions present during tumour growth, whereby IL-10 inhibited PDL1 and tumour cell apoptosis.

Conclusions

These new findings suggest that IL-10 counteracts IFN-γ effects on PD1/PDL1 pathway, resulting in possible resistance of the tumour to anti-PD1/PDL1 immunotherapy.

SUBMITTER: Vahl JM

PROVIDER: S-EPMC5729436 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Interleukin-10-regulated tumour tolerance in non-small cell lung cancer.

Vahl Julius Malte JM Friedrich Juliane J Mittler Susanne S Trump Sonja S Heim Lisanne L Kachler Katerina K Balabko Liubov L Fuhrich Nicole N Geppert Carol-Immanuel CI Trufa Denis Iulian DI Sopel Nina N Rieker Ralf R Sirbu Horia H Finotto Susetta S

British journal of cancer 20171010 11

<h4>Background</h4>Lung cancer is the most life-threatening cancer type worldwide. Treatment options include surgery, radio- and chemotherapy, as well as the use of immunomodulatory antibodies. Interleukin (IL)-10 is an immunosuppressive cytokine involved in tumour immune escape.<h4>Methods</h4>Immunohistochemistry (IHC) on human lung surgery tissue as well as human tumour cell line cultures, FACS analysis, real-time PCR and experimental lung cancer.<h4>Results</h4>Here we discovered a positive ...[more]

PMID: 29016555

Similar Datasets

Project description:BackgroundImmune checkpoint inhibitors (ICIs) brought about a major paradigm shift in non-small cell lung cancer (NSCLC) treatment. However, the use of ICIs is related to an unforeseeable pattern of immune-related adverse events (irAEs). Hence, more precise biomarkers are needed to predict the incidence of irAEs to prevent overtreatment of ICIs and decrease occurrences of irAEs. This study was designed to identify capable clinical features and plasma inflammatory factors for predicting irAEs.MethodsA total of 67 patients who received ICI monotherapy or ICI-based combination therapy were retrospectively identified. Clinical characteristics and plasma inflammatory cytokines were collected and analyzed to screen potential biological markers associated with irAEs. The chi-square test, Fisher's test, and the Mann-Whitney U test were performed for the primary analysis. The optimal cutoff value was determined by a receiver operating characteristic (ROC) curve. Univariate and multivariate logistic regression models were used to identify risk factors of irAEs. Univariate and multivariate Cox proportional hazards were also performed.ResultsOut of 67 patients, 40 (59.7%) experienced irAEs, and 7 (10.4%) experienced severe adverse events (grade ≥ 3). Among these analyzed immune profile biomarkers, only interleukin-10 (IL-10) was related to the risk of irAEs. A high baseline IL-10 plasma level (odds ratio (OR) = 5.318, 95% CI 1.174-24.081, p = 0.030) was found to be a tremendous and independent risk factor for the development of irAEs. Also, for the dynamic analysis, upregulation of IL-10 after one cycle of ICI treatment was positively related to the occurrence of irAEs (OR = 5.712, 95% CI 1.088-29.993, p = 0.039). When pneumonitis, the most common irAEs, was analyzed, only baseline high-expression IL-10 was accompanied with the incidence of pneumonitis (OR = 9.969, 95% CI 1.144-86.843, p = 0.037).ConclusionBaseline and dynamic IL-10 plasma levels are tremendously and independently related to higher risk in the development of irAEs and could be utilized for medical practice to monitor adverse events in patients with ICI treatment.

Project description:BackgroundHypoxia is a hallmark of cancer and is associated with poor prognosis. However, the molecular mechanism by which hypoxia promotes tumor progression remains unclear. MicroRNAs dysregulation has been shown to play a critical role in the tumor and tumor microenvironment. Here, we investigated the roles of miR-495 and miR-5688 in human non-small cell lung cancer (NSCLC) and their underlying mechanism.MethodsThe expression levels of miR-495 and miR-5688 in human NSCLC tissue specimens were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Deferoxamine (DFO) was used to determine whether the regulation of miR-495 and miR-5688 under hypoxia was dependent on hypoxia-inducible factor 1-alpha (HIF-1α). Furthermore, the functions of miR-495 and miR-5688 in tumor progression were evaluated using colony formation, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS), wound healing, transwell assays, and xenograft model. Two algorithms, PicTAR and Targetscan, were used to predict the target gene of these two miRNAs, and dual-luciferase reporter assay was conducted to confirm the target. The unpaired two-tailed t test, Pearson correlation analysis, and Fisher's exact probability test were performed for statistical analyses.ResultsTwo miRNAs, miR-495 and miR-5688, were found to participate in NSCLC progression under hypoxia. They were down-regulated in NSCLC tissues compared with normal tissues. We determined that hypoxia led to the down-regulation of miR-495 and miR-5688 in NSCLC cells, which was independent of HIF-1α and cellular metabolic energy. In addition, miR-495 and miR-5688 suppressed cell proliferation, migration, and invasion in vitro. The NSCLC xenograft model showed that miR-495 and miR-5688 inhibited tumor formation in vivo. Interestingly, we found that miR-495 and miR-5688 had the same target, interleukin-11 (IL-11). Recombinant human IL-11 counteracted the effects of miR-495 and miR-5688 on NSCLC cells, suggesting that miR-495 and miR-5688 executed their tumor suppressive role by repressing IL-11 expression.ConclusionWe found that hypoxia down-regulated the expression levels of miR-495 and miR-5688 in NSCLC to enhance IL-11 expression and tumor progression, indicating that the miR-495/miR-5688/IL-11 axis may serve as a therapeutic target and potential biomarker for NSCLC.

Dataset Information

Interleukin-10-regulated tumour tolerance in non-small cell lung cancer.

Background

Methods

Results

Conclusions

Publications

Interleukin-10-regulated tumour tolerance in non-small cell lung cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets