Expansion of Spleen Myeloid Suppressor Cells Represses NK Cell Cytotoxicity in Tumor Bearing Host (49.13)
| Autor: | Cunren Liu, Shaohua Yu, Kurt Zinn, Jianhua Wang, William E Grizzle, John Kappes, Huang-Ge Zhang |
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| Rok vydání: | 2007 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 178:S85-S85 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Tumor growth promotes the expansion of myeloid suppressor cells. An inverse correlation between natural killer (NK) cell activation and myeloid suppressor cell expansion in tumor-bearing patients and mice prompted us to investigate the role of myeloid suppressor cells in controlling NK cell antitumor cytotocixity. In TS/A breast tumor model, the in vivo NK cell cytotoxicity was impaired in tumor-bearing mice. After adoptive transfer to naive recipients, CD11b+Gr-1+ myeloid suppressor cells freshly isolated from spleens of tumor-bearing mice but not naive mice were able to inhibit NK cell cytotoxicity. An in vivo imaging analysis indicated that the removal of tumors resulted in a significant increase in NK cell cytotoxicity in lung to eliminate injected YAC-1 cells. FACS analysis of the composition of lung leucocytes further indicated that the removal of tumors also lead to the reduction of CD11b+Gr-1+ myeloid suppressor cells accumulated in the lung. These data suggest that CD11b+Gr-1+ myeloid suppressor cells suppress NK cell cytotoxicity. The inhibition of NK cell cytotoxicity is cell-cell contact dependent. Inhibition of perforin but not granzyme B was responsible for myeloid suppressor cell-mediated inhibition of NK cell cytotoxicity. Western blot analyses further suggested that myeloid suppressor cells suppress IL-2 mediated NK cell cytotoxicity by affecting the activity of Stat5. |
| Databáze: | OpenAIRE |
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