| First Author | Sinha P | Year | 2012 |
| Journal | Eur J Immunol | Volume | 42 |
| Issue | 8 | Pages | 2052-9 |
| PubMed ID | 22673957 | Mgi Jnum | J:187851 |
| Mgi Id | MGI:5438452 | Doi | 10.1002/eji.201142230 |
| Citation | Sinha P, et al. (2012) Tumor-induced myeloid-derived suppressor cell function is independent of IFN-gamma and IL-4Ralpha. Eur J Immunol 42(8):2052-9 |
| abstractText | Myeloid-derived suppressor cells (MDSCs) are present in most cancer patients and experimental animals where they exert a profound immune suppression and are a significant obstacle to immunotherapy. IFN-gamma and IL-4 receptor alpha (IL-4Ralpha) have been implicated as essential molecules for MDSC development and immunosuppressive function. If IFN-gamma and IL-4Ralpha are critical regulators of MDSCs, then they are potential targets for preventing MDSC accumulation or inhibiting MDSC function. Because data supporting a role for IFN-gamma and IL-4Ralpha are not definitive, we have examined MDSCs induced in IFN-gamma-deficient, IFN-gammaR-deficient, and IL-4Ralpha-deficient mice carrying three C57BL/6-derived (B16 melanoma, MC38 colon carcinoma, and 3LL lung adenocarcinoma), and three BALB/c-derived (4T1 and TS/A mammary carcinomas, and CT26 colon carcinoma) tumors. We report that although MDSCs express functional IFN-gammaR and IL-4Ralpha, and have the potential to signal through the STAT1 and STAT6 pathways, respectively, neither IFN-gamma nor IL-4Ralpha impacts the phenotype, accumulation, or T-cell suppressive potency of MDSCs, although IFN-gamma and IL-4Ralpha modestly alter MDSC-macrophage IL-10 crosstalk. Therefore, neither IFN-gamma nor IL-4Ralpha is a key regulator of MDSCs and targeting these molecules is unlikely to significantly alter MDSC accumulation or function. |
