| First Author | Liao W | Year | 2019 |
| Journal | Cancer Cell | Volume | 35 |
| Issue | 4 | Pages | 559-572.e7 |
| PubMed ID | 30905761 | Mgi Jnum | J:274207 |
| Mgi Id | MGI:6295099 | Doi | 10.1016/j.ccell.2019.02.008 |
| Citation | Liao W, et al. (2019) KRAS-IRF2 Axis Drives Immune Suppression and Immune Therapy Resistance in Colorectal Cancer. Cancer Cell 35(4):559-572.e7 |
| abstractText | The biological functions and mechanisms of oncogenic KRAS(G12D) (KRAS( *)) in resistance to immune checkpoint blockade (ICB) therapy are not fully understood. We demonstrate that KRAS( *) represses the expression of interferon regulatory factor 2 (IRF2), which in turn directly represses CXCL3 expression. KRAS( *)-mediated repression of IRF2 results in high expression of CXCL3, which binds to CXCR2 on myeloid-derived suppressor cells and promotes their migration to the tumor microenvironment. Anti-PD-1 resistance of KRAS( *)-expressing tumors can be overcome by enforced IRF2 expression or by inhibition of CXCR2. Colorectal cancer (CRC) showing higher IRF2 expression exhibited increased responsiveness to anti-PD-1 therapy. The KRAS( *)-IRF2-CXCL3-CXCR2 axis provides a framework for patient selection and combination therapies to enhance the effectiveness of ICB therapy in CRC. |
