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Cellular and cytokine-dependent immunosuppressive mechanisms of grm1-transgenic murine melanoma

Please always quote using this URN: urn:nbn:de:bvb:20-opus-125096
  • Grm1-transgenic mice spontaneously develop cutaneous melanoma. This model allowed us to scrutinize the generic immune responses over the course of melanoma development. To this end, lymphocytes obtained from spleens, unrelated lymph nodes and tumor-draining lymph nodes of mice with no evidence of disease, and low or high tumor burden were analyzed ex vivo and in vitro. Thereby, we could demonstrate an increase in the number of activated CD4\(^+\) and CD8+ lymphocytes in the respective organs with increasing tumor burden. However, mainlyGrm1-transgenic mice spontaneously develop cutaneous melanoma. This model allowed us to scrutinize the generic immune responses over the course of melanoma development. To this end, lymphocytes obtained from spleens, unrelated lymph nodes and tumor-draining lymph nodes of mice with no evidence of disease, and low or high tumor burden were analyzed ex vivo and in vitro. Thereby, we could demonstrate an increase in the number of activated CD4\(^+\) and CD8+ lymphocytes in the respective organs with increasing tumor burden. However, mainly CD4\(^+\) T cells, which could constitute both T helper as well as immunosuppressive regulatory T cells, but not CD8\(^+\) T cells, expressed activation markers upon in vitro stimulation when obtained from tumor-bearing mice. Interestingly, these cells from tumor-burdened animals were also functionally hampered in their proliferative response even when subjected to strong in vitro stimulation. Further analyses revealed that the increased frequency of regulatory T cells in tumor-bearing mice is an early event present in all lymphoid organs. Additionally, expression of the immunosuppressive cytokines TGF-β1 and IL-10 became more evident with increased tumor burden. Notably, TGF-β1 is strongly expressed in both the tumor and the tumor-draining lymph node, whereas IL-10 expression is more pronounced in the lymph node, suggesting a more complex regulation of IL-10. Thus, similar to the situation in melanoma patients, both cytokines as well as cellular immune escape mechanisms seem to contribute to the observed immunosuppressed state of tumor-bearing grm1-transgenic mice, suggesting that this model is suitable for preclinical testing of immunomodulatory therapeutics.show moreshow less

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Metadaten
Author: Miriam Alb, Christopher Sie, Christian Adam, Suzie Chen, Jürgen C. Becker, David Schrama
URN:urn:nbn:de:bvb:20-opus-125096
Document Type:Journal article
Faculties:Medizinische Fakultät / Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie
Language:English
Parent Title (English):Cancer Immunology, Immunotherapy
Year of Completion:2012
Volume:61
Issue:12
Pagenumber:2239-2249
Source:Cancer Immunology Immunotherapy (2012) 61:2239–2249 DOI 10.1007/s00262-012-1290-9
DOI:https://doi.org/10.1007/s00262-012-1290-9
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 616 Krankheiten
Tag:immune suppression; melanoma; regulatory T cell; tumor-draining lymph node
Release Date:2016/07/11
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung