| First Author | Hong Y | Year | 2015 |
| Journal | Cancer Res | Volume | 75 |
| Issue | 4 | Pages | 656-665 |
| PubMed ID | 25568183 | Mgi Jnum | J:218898 |
| Mgi Id | MGI:5619008 | Doi | 10.1158/0008-5472.CAN-14-2377 |
| Citation | Hong Y, et al. (2015) beta-Catenin Promotes Regulatory T-cell Responses in Tumors by Inducing Vitamin A Metabolism in Dendritic Cells. Cancer Res 75(4):656-65 |
| abstractText | Tumors actively suppress antitumor immunity, creating formidable barriers to successful cancer immunotherapy. The molecular mechanisms underlying tumor-induced immune tolerance are largely unknown. In the present study, we show that dendritic cells (DC) in the tumor microenvironment acquire the ability to metabolize vitamin A to produce retinoic acid (RA), which drives regulatory T-cell responses and immune tolerance. Tolerogenic responses were dependent on induction of vitamin A-metabolizing enzymes via the beta-catenin/T-cell factor (TCF) pathway in DCs. Consistent with this observation, DC-specific deletion of beta-catenin in mice markedly reduced regulatory T-cell responses and delayed melanoma growth. Pharmacologic inhibition of either vitamin A-metabolizing enzymes or the beta-catenin/TCF4 pathway in vivo had similar effects on tumor growth and regulatory T-cell responses. Hence, beta-catenin/TCF4 signaling induces local regulatory DC and regulatory T-cell phenotypes via the RA pathway, identifying this pathway as an important target for anticancer immunotherapy. Cancer Res; 75(4); 656-65. (c)2015 AACR. |
