scholarly journals PINK1 REGULATES PD-L1 AND MHC-I EXPRESSION IN LUNG CANCER WITH GLYCOLYTIC PHENOTYPE

Respirology ◽  
2018 ◽  
Vol 23 ◽  
pp. 294-294
Keyword(s):  
Lung Cancer ◽  
Mhc I ◽  
Glycolytic Phenotype

The correlation between immune status of patients and their prognosis in non-small cell lung cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23192-e23192
Author(s):  
Xiao Ding ◽  
Jiuwei Cui ◽  
Xu Yan ◽  
Chao Niu ◽  
Huimin Tian
Keyword(s):  
Lung Cancer ◽  
Poor Prognosis ◽  
Immune Status ◽  
Serum Samples ◽  
Mhc I ◽  
Expression Levels ◽  
Surface Molecules ◽  
Tnf Α ◽  
Ifn Γ ◽  
Nsclc Patients

e23192 Background: In order to investigate the association of immune status with the prognosis in patients with lung cancer and to screen the potential prognostic markers, the immune status including the expression levels of tumor surface molecules, tumor infiltrating lymphocytes (TIL) and cytokines, sMICA and sMICB in serum were detected in this study. Methods: Tissue and serum samples of 125 patients with NSCLC were obtained from the First Hospital of Jilin Universtiy. 50 serum samples of healthy volunteers were obtained as controls. Surface molecules of cancer cell, such as MHC-I, PD-L1, MICA/B and CD8+ TIL were detected with immunohistochemistry. Cytokines such as IL-2, IL-4, IL-6, IL-10, IFN-γ, TNF-α levels in serum were detected with Luminex. sMICA and sMICB levels were examined by ELISA. The association between their expression levels and patients’ prognosis was analyzed by SPSS 17.0 software. Results: MHC-I was down-expressed, PD-L1 and MICA/B were up-regulated in NSCLC. CD8+ TIL could be seen in tumor stroma and nest. In univariate analysis, we found that patients with down-expression of MHC-I and up-regulation of PD-L1 had a poor prognosis (P < 0.05). MICA/B expression had no correlation with patients’ prognosis (P > 0.05). Patients with more stromal CD8+ TIL might have better prognosis. In multivariate analysis, we found that MHC-I and stromal CD8+ TIL might be independent prognostic factors in NSCLC (P < 0.05). TNF-α and IFN-γ were significantly decreased, IL-6 was increased in NSCLC patients (P < 0.05). There were no connections between the cytokines levels with patients’ prognosis (P > 0.05). Serum sMICA was significantly higher in NSCLC patients than healthy controls (P < 0.05). sMICB tented to be elevated in NSCLC compared with health controls, but there was no significant difference (P > 0.05). High sMICA expression had an association with poor prognosis (P < 0.05). There was no connection between the sMICB level with patients’ prognosis (P > 0.05). Conclusions: The immune status of patients with NSCLC had a close association with their prognosis in this study. It worths further study to confirm the clinical value of MHC-I expression, stromal CD8+ TIL and serum sMICA as prognostic marker in the patients with NSCLC.

scholarly journals Relationship Between Neuroendocrine and Immune Gene Expression in Small Cell Lung Cancer

2020 ◽  
Author(s):  
Ling Cai ◽  
Hongyu Liu ◽  
fang huang ◽  
Junya Fujimoto ◽  
Luc Girard ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Neuroendocrine Cells ◽  
Immune Gene ◽  
Small Cell Lung ◽  
Mhc I ◽  
Immune Gene Expression

Abstract Small cell lung cancer (SCLC) is classified as a high-grade neuroendocrine (NE) tumor, but a subset of SCLC has been termed “variant” due to the loss of NE characteristics. In this study, we computed NE scores for patient-derived SCLC cell lines and xenografts, as well as human tumors. We aligned NE properties with transcription factor-defined molecular subtypes. Then we investigated the different immune phenotypes associated with high and low NE scores. We found repression of immune response genes as a shared feature between classic SCLC and pulmonary neuroendocrine cells of the healthy lung. With loss of NE fate, variant SCLC tumors regain cell-autonomous immune gene expression and exhibit higher tumor-immune interactions. Pan-cancer analysis revealed this NE lineage-specific immune phenotype in other cancers. Additionally, we observed MHC I re-expression in SCLC upon development of chemoresistance. These findings provide a new framework to guide design of treatment regimens in SCLC.

Glycolytic phenotype of non-small cell lung cancer: Implication of anaerobic glycolysis on malignant potential

2005 ◽  
Vol 23 (16_suppl) ◽  
pp. 9634-9634 ◽  
Author(s):  
I. Yoshino ◽  
T. Kameyama ◽  
Y. Shikada ◽  
T. Kometani ◽  
D. Kawano ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Malignant Potential ◽  
Anaerobic Glycolysis ◽  
Small Cell Lung ◽  
Glycolytic Phenotype

scholarly journals Cancer cell-intrinsic expression of MHC II in lung cancer cell lines is actively restricted by MEK/ERK signaling and epigenetic mechanisms

2020 ◽  
Vol 8 (1) ◽  
pp. e000441 ◽  
Author(s):  
Alexander J Neuwelt ◽  
Abigail K Kimball ◽  
Amber M Johnson ◽  
Benjamin W Arnold ◽  
Bonnie L Bullock ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Nsclc Cell ◽  
Erk Signaling ◽  
Mhc I ◽  
Mek Inhibitors ◽  
Mhc Ii ◽  
Programmed Death ◽  
Mitogen Activated Protein

BackgroundProgrammed death 1/programmed death ligand 1 (PD-1/PD-L1) targeted immunotherapy affords clinical benefit in ~20% of unselected patients with lung cancer. The factor(s) that determine whether a tumor responds or fails to respond to immunotherapy remains an active area of investigation. We have previously defined divergent responsiveness of two KRAS-mutant cell lines to PD-1/PD-L1 blockade using an orthotopic, immunocompetent mouse model. Responsiveness to PD-1/PD-L1 checkpoint blockade correlates with an interferon gamma (IFNγ)-inducible gene signature and major histocompatibility complex class II (MHC II) expression by cancer cells. In the current study, we aim to identify therapeutic targets that can be manipulated in order to enhance cancer-cell-specific MHC II expression.MethodsResponsiveness to IFNγ and induction of MHC II expression was assessed after various treatment conditions in mouse and human non-small cell lung cancer (NSCLC) cell lines using mass cytometric and flow cytometric analysis.ResultsSingle-cell analysis using mass and flow cytometry demonstrated that IFNγ consistently induced PD-L1 and MHC class I (MHC I) across multiple murine and human NSCLC cell lines. In contrast, MHC II showed highly variable induction following IFNγ treatment both between lines and within lines. In mouse models of NSCLC, MHC II induction was inversely correlated with basal levels of phosphorylated extracellular signal-regulated kinase (ERK) 1/2, suggesting potential mitogen-activated protein (MAP) kinase-dependent antagonism of MHC II expression. To test this, cell lines were subjected to varying levels of stimulation with IFNγ, and assessed for MHC II expression in the presence or absence of mitogen-activated protein kinase kinase (MEK) inhibitors. IFNγ treatment in the presence of MEK inhibitors significantly enhanced MHC II induction across multiple lung cancer lines, with minimal impact on expression of either PD-L1 or MHC I. Inhibition of histone deacetylases (HDACs) also enhanced MHC II expression to a more modest extent. Combined MEK and HDAC inhibition led to greater MHC II expression than either treatment alone.ConclusionsThese studies emphasize the active inhibitory role that epigenetic and ERK signaling cascades have in restricting cancer cell-intrinsic MHC II expression in NSCLC, and suggest that combinatorial blockade of these pathways may engender new responsiveness to checkpoint therapies.

scholarly journals Radiotherapy activates autophagy to increase CD8+ T cell infiltration by modulating major histocompatibility complex class-I expression in non-small cell lung cancer

2019 ◽  
Vol 47 (8) ◽  
pp. 3818-3830 ◽  
Author(s):  
Hai Zeng ◽  
Weijia Zhang ◽  
Yan Gong ◽  
Conghua Xie
Keyword(s):  
Lung Cancer ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
Small Cell ◽  
Cell Infiltration ◽  
Complex Class ◽  
Small Cell Lung ◽  
Mhc I ◽  
T Cell Infiltration ◽  
Histocompatibility Complex

Objective Radiotherapy is reported to enhance immune responses in cancer, but appropriate doses and mechanisms remain to be investigated. This study explored whether autophagy is involved in the regulation of major histocompatibility complex class I (MHC-I) expression and CD8+ T cell infiltration at different radiation doses. Methods Non-small cell lung cancer (NSCLC) cell lines A549 and H1975 were exposed to different doses of radiation. The levels of autophagy and MHC-I expression were examined 6 hours after irradiation. The effects of the autophagy inhibitor chloroquine (CQ) on MHC-I expression were also investigated, as well as the relationship between autophagy and MHC-1 expression. Pathological specimens from 69 NSCLC patients were collected, and immunohistochemistry was used to detect MHC-1 expression and CD8+ T cell infiltration in tumors. Results Irradiation induced autophagy and MHC-I expression during a single radiation dose from 2 to 20 Gy in a dose-dependent manner. CQ downregulated MHC-I expression. Immunohistochemistry indicated that MHC-I levels were positively correlated with the infiltration of CD8+ T cells in NSCLC cells (R2 = 0.713). Conclusions Autophagy induced MHC-I expression and increased CD8+ T cell infiltration. A single radiation dose of 20 Gy induced the strongest CD8+ T cell infiltration.

scholarly journals Relationship Between Neuroendocrine and Immune Gene Expression in Small Cell Lung Cancer

2020 ◽  
Author(s):  
Ling Cai ◽  
Hongyu Liu ◽  
Fang Huang ◽  
Junya Fujimoto ◽  
Luc Girard ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Neuroendocrine Cells ◽  
Immune Gene ◽  
Small Cell Lung ◽  
Mhc I ◽  
Immune Gene Expression

ABSTRACTSmall cell lung cancer (SCLC) is classified as a high-grade neuroendocrine (NE) tumor, but a subset of SCLC has been termed “variant” due to the loss of NE characteristics. In this study, we computed NE scores for patient-derived SCLC cell lines and xenografts, as well as human tumors. We aligned NE properties with transcription factor-defined molecular subtypes. Then we investigated the different immune phenotypes associated with high and low NE scores. We found repression of immune response genes as a shared feature between classic SCLC and pulmonary neuroendocrine cells of the healthy lung. With loss of NE fate, variant SCLC tumors regain cell-autonomous immune gene expression and exhibit higher tumor-immune interactions. Pan-cancer analysis revealed this NE lineage-specific immune phenotype in other cancers. Additionally, we observed MHC I re-expression in SCLC upon development of chemoresistance. These findings provide a new framework to guide design of treatment regimens in SCLC.

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