| First Author | Kusmartsev S | Year | 2005 |
| Journal | J Immunol | Volume | 174 |
| Issue | 8 | Pages | 4880-91 |
| PubMed ID | 15814715 | Mgi Jnum | J:109996 |
| Mgi Id | MGI:3630214 | Doi | 10.4049/jimmunol.174.8.4880 |
| Citation | Kusmartsev S, et al. (2005) STAT1 signaling regulates tumor-associated macrophage-mediated T cell deletion. J Immunol 174(8):4880-91 |
| abstractText | It is well established that tumor progression is associated with the accumulation of myeloid suppressive cells, which in mice include Gr-1+ immature myeloid cells and F4/80+ macrophages. The paradox is that with the exception of terminal stages of the disease or chemotherapy treatment, tumor-bearing mice or cancer patients do not display a profound systemic immune suppression. We therefore raised the question as to whether myeloid cell-mediated T cell suppression is controlled at a local level at the site of the tumor. We have demonstrated that after adoptive transfer to tumor-bearing recipients, Gr-1+ (immature myeloid cells) freshly isolated from spleens of tumor-bearing mice become F4/80+ tumor-associated macrophages (TAM). These TAM, but not F4/80+ macrophages or Gr-1+ cells freshly isolated from spleens of tumor-bearing or naive mice were able to inhibit T cell-mediated immune response in vitro via induction of T cell apoptosis. Arginase and NO were both responsible for the apoptotic mechanism, and were seen only in TAM, but not in freshly isolated Gr1+ cells. Using the analysis of STAT activity in combination with STAT knockout mice, we have determined that STAT1, but not STAT3 or STAT6, was responsible for TAM-suppressive activity. |
