| First Author | Romieu-Mourez R | Year | 2010 |
| Journal | Cancer Res | Volume | 70 |
| Issue | 20 | Pages | 7742-7 |
| PubMed ID | 20924101 | Mgi Jnum | J:165567 |
| Mgi Id | MGI:4837768 | Doi | 10.1158/0008-5472.CAN-10-0296 |
| Citation | Romieu-Mourez R, et al. (2010) Mesenchymal stromal cells expressing ErbB-2/neu elicit protective antibreast tumor immunity in vivo, which is paradoxically suppressed by IFN-{gamma} and tumor necrosis factor-{alpha} priming. Cancer Res 70(20):7742-7 |
| abstractText | It is unknown whether mesenchymal stromal cells (MSC) can regulate immune responses targeting tumor autoantigens of low immunogenicity. We tested here whether immunization with MSC could break immune tolerance towards the ErbB-2/HER-2/neu tumor antigen and the effects of priming with IFN-gamma and tumor necrosis factor-alpha (TNF-alpha) on this process. BALB/c- and C57BL/6-derived MSC were lentivirally transduced to express a kinase-inactive rat neu mutant (MSC/Neu). Immunization of BALB/c mice with nontreated or IFN-gamma-primed allogeneic or syngeneic MSC/Neu induced similar levels of anti-neu antibody titers; however, only syngeneic MSC/Neu induced protective neu-specific CD8(+) T cell responses. Compared to immunization with nontreated or IFN-gamma-primed syngeneic MSC/Neu, the number of circulating neu-specific CD8(+) T cells and titers of anti-neu antibodies were observed to be decreased after immunizations with IFN-gamma- plus TNF-alpha-primed MSC/Neu. In addition, syngeneic MSC/Neu seemed more efficient than IFN-gamma-primed MSC/Neu at inducing a protective therapeutic antitumor immune response resulting in the regression of transplanted neu-expressing mammary tumor cells. In vitro antigen-presenting cell assays performed with paraformaldehyde-fixed or live MSC showed that priming with IFN-gamma plus TNF-alpha, compared to priming with IFN-gamma alone, increased antigen presentation as well as the production of immunosuppressive factors. These data suggest that whereas MSC could effectively serve as antigen-presenting cells to induce immune responses aimed at tumor autoantigens, these functions are critically regulated by IFN-gamma and TNF-alpha. |
