Th1 polarization in the tumor microenvironment upregulates the myeloid-derived suppressor-like function of macrophages
| Autor: | Masanao Saio, Takao Takahashi, Kazuhiro Yoshida, Shinji Osada, Naoki Umemura, Kenichi Nonaka, Arizumi Kikuchi |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Tumor microenvironment medicine.medical_treatment Nitrotyrosine Macrophages Myeloid-Derived Suppressor Cells Immunology Immunotherapy Neoplasms Experimental Biology Th1 Cells Arginase Mice Inbred C57BL chemistry.chemical_compound Mice Immune system chemistry medicine Cancer research Tumor Microenvironment Macrophage Cytotoxic T cell Animals Tumor Escape CD8 |
| Zdroj: | Cellular immunology. 369 |
| ISSN: | 1090-2163 |
| Popis: | Here, we investigated the effect of Th1 polarization in the tumor microenvironment (TME) on tumor-associated macrophage (TAM) maturation and activation. In our immunotherapy mouse model, with a Th1-dominant TME, tumors regressed in all cases, with complete regression in 80% of the cases. Monocyte-derived dendritic cells and activated CD4+ and CD8+T-cells increased in the tumor-draining lymph node, and correlated with each other in the therapeutic model. However, the cytotoxicity of tumor-infiltrating CD8+T-cells was slightly inhibited, whereas the number of T-cells significantly increased. Moreover, the number of TAMs increased; their maturation was inhibited; and nitrotyrosine (NT) production, as well as iNOS and arginase I expression, was increased, suggestive of the myeloid-derived suppressor cell-like immunosuppressive function of TAMs. IFN-γ knockout in the therapeutic model decreased NT production and induced macrophage maturation. Hence, Th1 polarization in the IFN-γ-dominant condition induces T-cell immune responses; however, it also enhances the immunosuppressive activity of TAMs. |
| Databáze: | OpenAIRE |
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