Treatment-Enhanced CD4+Foxp3+ Glucocorticoid-Induced TNF Receptor Family RelatedHigh Regulatory Tumor-Infiltrating T Cells Limit the Effectiveness of Cytokine-Based Immunotherapy
| العنوان: | Treatment-Enhanced CD4+Foxp3+ Glucocorticoid-Induced TNF Receptor Family RelatedHigh Regulatory Tumor-Infiltrating T Cells Limit the Effectiveness of Cytokine-Based Immunotherapy |
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| المؤلفون: | Jian Huang, Aklile Berhanu, Hideho Okada, Walter J. Storkus, Simon C. Watkins |
| المصدر: | The Journal of Immunology. 178:3400-3408 |
| بيانات النشر: | The American Association of Immunologists, 2007. |
| سنة النشر: | 2007 |
| مصطلحات موضوعية: | Antigens, Differentiation, T-Lymphocyte, T cell, Immunology, chemical and pharmacologic phenomena, CD8-Positive T-Lymphocytes, Biology, Lymphocyte Activation, T-Lymphocytes, Regulatory, Inducible T-Cell Co-Stimulator Protein, Mice, Interleukin 21, Lymphocytes, Tumor-Infiltrating, Antigen, Antigens, CD, Cell Line, Tumor, Glucocorticoid-Induced TNFR-Related Protein, medicine, Animals, Immunology and Allergy, Cytotoxic T cell, IL-2 receptor, Cell Proliferation, Mice, Inbred BALB C, ZAP70, Membrane Proteins, FOXP3, Forkhead Transcription Factors, hemic and immune systems, Neoplasms, Experimental, medicine.anatomical_structure, Cancer research, Cytokines, Immunotherapy, Immunologic Memory, CD8, Signal Transduction |
| الوصف: | Regulatory T cells can suppress activated CD4+ and CD8+ T effector cells and may serve as an impediment to spontaneous or therapeutic type 1 antitumor immunity. In a previous study, we observed minimal therapeutic impact, but significantly enhanced T cell cross-priming and lesional infiltration of tumor-reactive CD8+ T cells into established CMS4 sarcomas after combined treatment of BALB/c mice with rFLt3 ligand (rFL) and recombinant GM-CSF (rGM-CSF). In this study, we show that this cytokine regimen also results in the profound enhancement of CD4+ tumor-infiltrating lymphocytes (TIL) expressing FoxP3, IL-10, and TGF-β mRNA, with 50 or 90% of CD4+ TIL coexpressing the CD25 and glucocorticoid-induced TNFR family related molecules, respectively. Intracellular staining for Foxp3 protein revealed that combined treatment with rFL plus rGM-CSF results in a significant increase in CD4+Foxp3+ T cells in the spleen of both control and tumor-bearing mice, and that nearly half of CD4+ TIL expressed this marker. In addition, CD4+ TIL cells were of an activated/memory (ICOShighCD62LlowCD45RBlow) phenotype and were capable of suppressing allospecific T cell proliferation and IFN-γ production from (in vivo cross-primed) anti-CMS4 CD8+ T cells in vitro, via a mechanism at least partially dependent on IL-10 and TGF-β. Importantly, in vivo depletion of CD4+ T cells resulted in the ability of previously ineffective, rFL plus rGM-CSF therapy-induced CD8+ T cells to now mediate tumor regression. |
| تدمد: | 1550-6606 0022-1767 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::eff40496b9151c0048a59159db46d1e6Test https://doi.org/10.4049/jimmunol.178.6.3400Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....eff40496b9151c0048a59159db46d1e6 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15506606 00221767 |
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