Therapeutic T cells induce tumor-directed chemotaxis of innate immune cells through tumor-specific secretion of chemokines and stimulation of B16BL6 melanoma to secrete chemokines
| العنوان: | Therapeutic T cells induce tumor-directed chemotaxis of innate immune cells through tumor-specific secretion of chemokines and stimulation of B16BL6 melanoma to secrete chemokines |
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| المؤلفون: | Matthias Schiller, Bernard A. Fox, Natasja K. van den Engel, J. Schmidt, F. Löhe, Christian H. Poehlein, Dominik Rüttinger, Hauke Winter, Rudolf Hatz, Hong-Ming Hu, Karl-Walter Jauch |
| المصدر: | Journal of Translational Medicine, Vol 5, Iss 1, p 56 (2007) Journal of Translational Medicine |
| بيانات النشر: | BMC, 2007. |
| سنة النشر: | 2007 |
| مصطلحات موضوعية: | Chemokine, Adoptive cell transfer, T-Lymphocytes, medicine.medical_treatment, T cell, Melanoma, Experimental, lcsh:Medicine, Nitric Oxide, General Biochemistry, Genetics and Molecular Biology, Interferon-gamma, Mice, 03 medical and health sciences, Interleukin 21, 0302 clinical medicine, Antigen, Cell Movement, Neoplasms, medicine, Animals, Neoplasm Metastasis, 030304 developmental biology, Mice, Knockout, Medicine(all), 0303 health sciences, Innate immune system, biology, Biochemistry, Genetics and Molecular Biology(all), Chemotaxis, Macrophages, Research, lcsh:R, General Medicine, Immunotherapy, Adoptive Transfer, 3. Good health, Mice, Inbred C57BL, medicine.anatomical_structure, Immunology, Chemokine secretion, biology.protein, Cancer research, Female, Chemokines, 030215 immunology |
| الوصف: | Background The mechanisms by which tumor-specific T cells induce regression of established metastases are not fully characterized. In using the poorly immunogenic B16BL6-D5 (D5) melanoma model we reported that T cell-mediated tumor regression can occur independently of perforin, IFN-γ or the combination of both. Characterization of regressing pulmonary metastases identified macrophages as a major component of the cells infiltrating the tumor after adoptive transfer of effector T cells. This led us to hypothesize that macrophages played a central role in tumor regression following T-cell transfer. Here, we sought to determine the factors responsible for the infiltration of macrophages at the tumor site. Methods These studies used the poorly immunogenic D5 melanoma model. Tumor-specific effector T cells, generated from tumor vaccine-draining lymph nodes (TVDLN), were used for adoptive immunotherapy and in vitro analysis of chemokine expression. Cellular infiltrates into pulmonary metastases were determined by immunohistochemistry. Chemokine expression by the D5 melanoma following co-culture with T cells, IFN-γ or TNF-α was determined by RT-PCR and ELISA. Functional activity of chemokines was confirmed using a macrophage migration assay. T cell activation of macrophages to release nitric oxide (NO) was determined using GRIES reagent. Results We observed that tumor-specific T cells with a type 1 cytokine profile also expressed message for and secreted RANTES, MIP-1α and MIP-1β following stimulation with specific tumor. Unexpectedly, D5 melanoma cells cultured with IFN-γ or TNF-α, two type 1 cytokines expressed by therapeutic T cells, secreted Keratinocyte Chemoattractant (KC), MCP-1, IP-10 and RANTES and expressed mRNA for MIG. The chemokines released by T cells and cytokine-stimulated tumor cells were functional and induced migration of the DJ2PM macrophage cell line. Additionally, tumor-specific stimulation of wt or perforin-deficient (PKO) effector T cells induced macrophages to secrete nitric oxide (NO), providing an additional effector mechanism for T cell-mediated tumor regression. Conclusion These data suggest two possible sources for chemokine secretion that stimulates macrophage recruitment to the site of tumor metastases. Both appear to be initiated by T cell recognition of specific antigen, but one is dependent on the tumor cells to produce the chemokines that recruit macrophages. |
| اللغة: | English |
| تدمد: | 1479-5876 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ff374f8961229bc6bf62b457dceb950aTest http://www.translational-medicine.com/content/5/1/56Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....ff374f8961229bc6bf62b457dceb950a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14795876 |
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