Direct T cell–tumour interaction triggers TH1 phenotype activation through the modification of the mesenchymal stromal cells transcriptional programme
| Autor: | Yuanlong Zhao, F. M. Marincola, Davide Bedognetti, David F. Stroncek, Marianna Sabatino, Huan Wang, Jianjian Jin, V. De Giorgi, Ping Jin, Sara Civini, Jiansong Ren |
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| Rok vydání: | 2014 |
| Předmět: |
Cancer Research
Skin Neoplasms Cellular differentiation T cell Bone Marrow Cells Biology Interleukin-12 Subunit p35 MSC Lymphocytes Tumor-Infiltrating Cell Line Tumor HLA-A2 Antigen Tumor Microenvironment medicine Humans Indoleamine-Pyrrole 2 3 -Dioxygenase Melanoma Molecular Diagnostics Cell Proliferation Regulation of gene expression Tumor microenvironment Cell growth Gene Expression Profiling Mesenchymal stem cell Cell Differentiation Mesenchymal Stem Cells Th1 Cells Phenotype Coculture Techniques Cell biology Gene Expression Regulation Neoplastic medicine.anatomical_structure TH1 phenotype Oncology Cell culture Immunology Cytokines tumour microenvironment |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| DOI: | 10.1038/bjc.2014.235 |
| Popis: | Background: Mesenchymal stromal cells (MSCs) are heterogeneous cells with immunoregulatory and wound-healing properties. In cancer, they are known to be an essential part of the tumour microenvironment. However, their role in tumour growth and rejection remains unclear. To investigate this, we co-cultured human MSCs, tumour infiltrating lymphocytes (TIL), and melanoma cells to investigate the role of MSCs in the tumour environment. Methods: Mesenchymal stromal cells were co-cultured with melanoma antigen-specific TIL that were stimulated either with HLA-A*0201+ melanoma cells or with a corresponding clone that had lost HLA-A*0201 expression. Results: Activated TIL induced profound pro-inflammatory gene expression signature in MSCs. Analysis of culture supernatant found that MSCs secreted pro-inflammatory cytokines, including TH1 cytokines that have been previously associated with immune-mediated antitumor responses. In addition, immunohistochemical analysis on selected markers revealed that the same activated MSCs secreted both the TH1 cytokine (interleukin-12) and indoleamine 2,3 dioxygenase (IDO), a classical immunosuppressive factor. Conclusions: This study reflected that the plasticity of MSCs is highly dependent upon microenvironment conditions. Tumour-activated TIL induced TH1 phenotype change in MSCs that is qualitatively similar to the previously described immunologic constant of rejection signature observed during immune-mediated, tissue-specific destruction. This response may be responsible for the in loco amplification of antigen-specific anti-cancer immune response. |
| Databáze: | OpenAIRE |
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