Tumor Cell-Released TLR4 Ligands Stimulate Gr-1+CD11b+F4/80+ Cells to Induce Apoptosis of Activated T Cells
| Autor: | Dong Li, Zhi-Hui Liang, Ye Yuan, Yan-Yan Liu, Zhang Lei, Yong Xu, Jing-Jing Wei, Ling-Cong Sun, Hui-Fen Zhu, Bin Yan, Zuo-Hua Feng, Bo Li, Sheng-Jun Liao, Chuan-Wang Song, Gui-Mei Zhang |
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| Rok vydání: | 2010 |
| Předmět: |
Carcinoma
Hepatocellular medicine.medical_treatment Immunology Apoptosis Biology Ligands Lymphocyte Activation Monocytes Mice Necrosis T-Lymphocyte Subsets Cell Line Tumor medicine Animals Immunology and Allergy Macrophage STAT3 Receptor Cells Cultured Mice Inbred BALB C CD11b Antigen Epidermal Growth Factor Liver Neoplasms Immunotherapy Molecular biology Cell biology Toll-Like Receptor 4 Arginase Cell culture biology.protein Receptors Chemokine Signal transduction Apoptosis Regulatory Proteins Signal Transduction |
| Zdroj: | The Journal of Immunology. 185:2773-2782 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Gr-1(+)CD11b(+)F4/80(+) cells play important roles in tumor development and have a negative effect on tumor immunotherapy. So far, the mechanisms underlying the regulation of their immunosuppressive phenotype by classical and alternative macrophage activation stimuli are not well elucidated. In this study, we found that molecules from necrotic tumor cells (NTC-Ms) stimulated Gr-1(+)CD11b(+)F4/80(+) cells to induce apoptosis of activated T cells but not nonstimulated T cells. The apoptosis-inducing capacity was determined by higher expression levels of arginase I and IL-10 relative to those of NO synthase 2 and IL-12 in Gr-1(+)CD11b(+)F4/80(+) cells, which were induced by NTC-Ms through TLR4 signaling. The apoptosis-inducing capacity of NTC-Ms-stimulated Gr-1(+)CD11b(+)F4/80(+) cells could be enhanced by IL-10. IFN-gamma may reduce the apoptosis-inducing capacity of Gr-1(+)CD11b(+)F4/80(+) cells only if their response to IFN-gamma was not attenuated. However, the potential of Gr-1(+)CD11b(+)F4/80(+) cells to express IL-12 in response to IFN-gamma could be attenuated by tumor, partially due to the existence of active STAT3 in Gr-1(+)CD11b(+)F4/80(+) cells and NTC-Ms from tumor. In this situation, IFN-gamma could not effectively reduce the apoptosis-inducing capacity of Gr-1(+)CD11b(+)F4/80(+) cells. Tumor immunotherapy with 4-1BBL/soluble programmed death-1 may significantly reduce, but not abolish the apoptosis-inducing capacity of Gr-1(+)CD11b(+)F4/80(+) cells in local microenvironment. Blockade of TLR4 signaling could further reduce the apoptosis-inducing capacity of Gr-1(+)CD11b(+)F4/80(+) cells and enhance the suppressive effect of 4-1BBL/soluble form of programmed death-1 on tumor growth. These findings indicate the relationship of distinct signaling pathways with apoptosis-inducing capacity of Gr-1(+)CD11b(+)F4/80(+) cells and emphasize the importance of blocking TLR4 signaling to prevent the induction of T cell apoptosis by Gr-1(+)CD11b(+)F4/80(+) cells. |
| Databáze: | OpenAIRE |
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