| First Author | Nonaka K | Year | 2021 |
| Journal | Cell Immunol | Volume | 369 |
| Pages | 104437 | PubMed ID | 34530344 |
| Mgi Jnum | J:312909 | Mgi Id | MGI:6792495 |
| Doi | 10.1016/j.cellimm.2021.104437 | Citation | Nonaka K, et al. (2021) Th1 polarization in the tumor microenvironment upregulates the myeloid-derived suppressor-like function of macrophages. Cell Immunol 369:104437 |
| abstractText | 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-gamma knockout in the therapeutic model decreased NT production and induced macrophage maturation. Hence, Th1 polarization in the IFN-gamma-dominant condition induces T-cell immune responses; however, it also enhances the immunosuppressive activity of TAMs. |
