Abstract 583: DNA demethylating agents enhance susceptibility of lung cancer cells to γδ T cell-based immunotherapy via MHC-independent mechanisms

2019 ◽  
Author(s):  
Rueyhung Weng ◽  
Chien-Ting Lin ◽  
Tai-Chung Huang ◽  
Hsuan-Hsuan Lu ◽  
Yi-Chieh Wu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cell ◽  
Cancer Cells ◽  
Lung Cancer Cells ◽  
Γδ T Cell ◽  
Demethylating Agents

scholarly journals Imperatorin Targets MCL-1 to Sensitize CD133+ Lung Cancer Cells to γδ-T Cell-Mediated Cytotoxicity

2018 ◽  
Vol 49 (1) ◽  
pp. 235-244 ◽  
Author(s):  
Changxuan You ◽  
Yu Yang ◽  
Beili Gao
Keyword(s):  
Lung Cancer ◽  
Flow Cytometry ◽  
T Cells ◽  
T Cell ◽  
Cancer Cells ◽  
Γδ T Cells ◽  
Lung Cancer Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Γδ T Cell ◽  
Cytochrome C Release

Background/Aims: CD133+ cancer cells display low sensitivity to anti-cancer treatment; thus, combination treatment with adjuvant drugs is required to improve the efficiency of cancer therapy. The aim of this study was to explore the effect of imperatorin, a linear furanocoumarin compound, on γδ T cell-mediated cytotoxicity against CD133+ lung cancer cells. Methods: CD133+ and CD133- subgroups from A549 and PC9 lung cancer cells were sorted by using flow cytometry. The cytotoxicity of γδ T cells against cancer cells was evaluated by measuring lactate dehydrogenase release. The concentration of tumor necrosis factor-related apoptosis-inducing ligand in the co-culture system was determined by using an enzyme-linked immunosorbent assay. Mitochondrial membrane potential, expression of death receptor 4 (DR4) and DR5 on the cell surface, and rate of apoptosis were measured by flow cytometry. Cytochrome c release and cellular protein expression were detected by western blot analysis. Results: Compared with CD133- cells, CD133+ cells were resistant to γδ T cell-mediated cytotoxicity. However, imperatorin significantly increased the sensitivity of CD133+ lung cancer cells to γδ T cell treatment in vitro and in vivo. Mechanically, we found that myeloid cell leukemia 1 (MCL-1), an important anti-apoptotic protein belonging to the Bcl-2 family, was overexpressed in CD133+ A549 and PC9 cells compared to their corresponding CD133- cells. Co-treatment with imperatorin and γδ T cells suppressed the expression of MCL-1, and thus promoted the mitochondrial apoptosis mediated by γδ T cells in CD133+ A549 and PC9 lung cancer cells. Conclusion: Up-regulated MCL-1 in CD133+ lung cancer cells is responsible for their resistance to γδ T cells. Furthermore, the combination of γδ T cells with imperatorin sensitized CD133+ lung cancer cells to γδ T cell-mediated cytotoxicity by targeting MCL-1.

Induced expression of B7-H3 on the lung cancer cells and macrophages suppresses T-cell mediating anti-tumor immune response

2013 ◽  
Vol 319 (1) ◽  
pp. 96-102 ◽  
Author(s):  
Cheng Chen ◽  
Yu Shen ◽  
Qiu-Xia Qu ◽  
Xu-Qin Chen ◽  
Xue-Guang Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Immune Response ◽  
T Cell ◽  
Cancer Cells ◽  
Lung Cancer Cells ◽  
Induced Expression

Dendritic cells efficiently acquire and present antigen derived from lung cancer cells and induce antigen-specific T-cell responses

2003 ◽  
Vol 52 (7) ◽  
pp. 413-422 ◽  
Author(s):  
Yaling Zhou ◽  
Julie A. McEarchern ◽  
Edward Howard ◽  
Gary Pestano ◽  
Michael L. Salgaller ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dendritic Cells ◽  
T Cell ◽  
Cancer Cells ◽  
T Cell Responses ◽  
Lung Cancer Cells ◽  
Cell Responses

scholarly journals Resveratrol induces PD-L1 expression through snail-driven activation of Wnt pathway in lung cancer cells

2021 ◽  
Author(s):  
Mengmeng Yang ◽  
Zongyu Li ◽  
Jianping Tao ◽  
Hao Hu ◽  
Zilin Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cell ◽  
Cancer Cells ◽  
Tumor Immunity ◽  
Immune Checkpoint ◽  
Wnt Pathway ◽  
Expression Patterns ◽  
Lung Cancer Cells ◽  
Luciferase Reporter ◽  
Therapeutic Effects

Abstract Purpose Recent clinical trials with agents targeting immune checkpoint pathway have emerged as an important therapeutic approach for a broad range of cancer types. Resveratrol has been shown to possess cancer preventive and therapeutic effects and has potential to be chemotherapeutic agent/adjuvant. Here, we assessed the effect of resveratrol on immune checkpoint pathways. Methods The expression patterns of Wnt components and PD-L1 were examined by Western blot, Chromatin immunoprecipitation (ChIP) was used for analysis of DNA–protein interaction, the promoter activity was determined by luciferase reporter assay, apoptosis was analyzed by flow cytometry and the ability of the resveratrol to modulate T cell function was assessed in a co-culture system. Results Although the dose-, and cell-type dependent effects of resveratrol on PD-L1 expression have been reported, we show here that resveratrol dose-dependently upregulates PD-L1 expression at the range of pharmacologic-achievable concentrations in lung cancer cells and that is essential for suppression of T-cell-mediated immune response. We also found that Wnt pathway is critical for mediating resveratrol-induced PD-L1 upregulation. Mechanistically, resveratrol activates SirT1 deacetylase to deacetylate and stabilize transcriptional factor Snail. Snail in turn inhibits transcription of Axin2, which leads in disassembly of destruction complex and enhanced binding of β-catenin/TCF to PD-L1 promoter. Conclusion We conclude that resveratrol is capable to suppress anti-tumor immunity by controlling mainly PD-L1 expression. This finding will extend the understanding of resveratrol in regulation of tumor immunity and is relevant to the debate on resveratrol supplements for lung cancer patients.

scholarly journals Epigenetic modulation of immune synaptic-cytoskeletal networks potentiates γδ T cell-mediated cytotoxicity in lung cancer

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Rueyhung R. Weng ◽  
Hsuan-Hsuan Lu ◽  
Chien-Ting Lin ◽  
Chia-Chi Fan ◽  
Rong-Shan Lin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
T Cell ◽  
Cancer Cells ◽  
T Cell Activation ◽  
Actin Polymerization ◽  
Γδ T Cells ◽  
Human Lung Cancer ◽  
Γδ T Cell ◽  
Cancer Management

Abstractγδ T cells are a distinct subgroup of T cells that bridge the innate and adaptive immune system and can attack cancer cells in an MHC-unrestricted manner. Trials of adoptive γδ T cell transfer in solid tumors have had limited success. Here, we show that DNA methyltransferase inhibitors (DNMTis) upregulate surface molecules on cancer cells related to γδ T cell activation using quantitative surface proteomics. DNMTi treatment of human lung cancer potentiates tumor lysis by ex vivo-expanded Vδ1-enriched γδ T cells. Mechanistically, DNMTi enhances immune synapse formation and mediates cytoskeletal reorganization via coordinated alterations of DNA methylation and chromatin accessibility. Genetic depletion of adhesion molecules or pharmacological inhibition of actin polymerization abolishes the potentiating effect of DNMTi. Clinically, the DNMTi-associated cytoskeleton signature stratifies lung cancer patients prognostically. These results support a combinatorial strategy of DNMTis and γδ T cell-based immunotherapy in lung cancer management.

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