| First Author | Liang X | Year | 2014 |
| Journal | J Leukoc Biol | Volume | 95 |
| Issue | 1 | Pages | 179-90 |
| PubMed ID | 24023259 | Mgi Jnum | J:209541 |
| Mgi Id | MGI:5568050 | Doi | 10.1189/jlb.0613330 |
| Citation | Liang X, et al. (2014) beta-catenin mediates tumor-induced immunosuppression by inhibiting cross-priming of CD8(+) T cells. J Leukoc Biol 95(1):179-90 |
| abstractText | Whereas CD8(+) T cells are essential for anti-tumor immunity, tumors often evade CD8(+) T cell surveillance by immunosuppression. As the initiators of antigen-specific immune responses, DCs are likely to play a central role in regulating the balance between immunity and tolerance to tumor antigens and are specialized in their ability to cross-present exogenous tumor antigens on MHC class I molecules to initiate CD8(+) T cell immunity. However, it remains unclear whether and how tumors modulate DC functions to suppress CD8(+) T cell responses. We have shown previously that beta-catenin signaling in DCs promotes DC-mediated CD8(+) T cell tolerance. Here, we tested the hypothesis that beta-catenin in DCs mediates tumor-induced suppression of CD8(+) T cell immunity by inhibiting the ability of DCs in cross-priming. beta-Catenin was activated in DCs by multiple tumors in vivo and in vitro. B16 melanoma-bearing mice, when vaccinated with DC-targeting anti-DEC-205 mAb fused with tumor antigens, exhibited dampened CD8(+) immunity, similar to DC-beta-catenin(active) mice. DCs from DC-beta-catenin(active) and tumor-bearing mice were deficient in cross-priming, and antigen-specific CD8(+) T cells primed in these mice resulted in dampened CD8(+) memory responses. Importantly, DC-beta-catenin(-)/(-) mice completely abrogate tumor-mediated inhibition of cross-priming, suggesting that tumor-induced inhibition of cross-priming is dependent on beta-catenin. Finally, enhancing cross-priming at the priming or recall phase rescued beta-catenin-suppressed CD8(+) immunity in DC-beta-catenin(active) and tumor-bearing mice. Thus, beta-catenin-mediated inhibition of cross-priming represents a new and potentially general mechanism that tumors employ to achieve immunosuppression. |
