| First Author | Tavazoie MF | Year | 2018 |
| Journal | Cell | Volume | 172 |
| Issue | 4 | Pages | 825-840.e18 |
| PubMed ID | 29336888 | Mgi Jnum | J:266110 |
| Mgi Id | MGI:6212700 | Doi | 10.1016/j.cell.2017.12.026 |
| Citation | Tavazoie MF, et al. (2018) LXR/ApoE Activation Restricts Innate Immune Suppression in Cancer. Cell 172(4):825-840.e18 |
| abstractText | Therapeutic harnessing of adaptive immunity via checkpoint inhibition has transformed the treatment of many cancers. Despite unprecedented long-term responses, most patients do not respond to these therapies. Immunotherapy non-responders often harbor high levels of circulating myeloid-derived suppressor cells (MDSCs)-an immunosuppressive innate cell population. Through genetic and pharmacological approaches, we uncovered a pathway governing MDSC abundance in multiple cancer types. Therapeutic liver-X nuclear receptor (LXR) agonism reduced MDSC abundance in murine models and in patients treated in a first-in-human dose escalation phase 1 trial. MDSC depletion was associated with activation of cytotoxic T lymphocyte (CTL) responses in mice and patients. The LXR transcriptional target ApoE mediated these effects in mice, where LXR/ApoE activation therapy elicited robust anti-tumor responses and also enhanced T cell activation during various immune-based therapies. We implicate the LXR/ApoE axis in the regulation of innate immune suppression and as a target for enhancing the efficacy of cancer immunotherapy in patients. |
