| First Author | Zhang Y | Year | 2020 |
| Journal | Mol Ther | Volume | 28 |
| Issue | 1 | Pages | 89-99 |
| PubMed ID | 31607540 | Mgi Jnum | J:316155 |
| Mgi Id | MGI:6834693 | Doi | 10.1016/j.ymthe.2019.09.019 |
| Citation | Zhang Y, et al. (2020) Neutrophils Deficient in Innate Suppressor IRAK-M Enhances Anti-tumor Immune Responses. Mol Ther 28(1):89-99 |
| abstractText | Tumor-associated immune-suppressive neutrophils are prevalent in various cancers, including colorectal cancer. However, mechanisms of immune-suppressive neutrophils are not well understood. We report that a key innate suppressor, IRAK-M (interleukin-1 receptor-associated kinase M), is critically involved in the establishment of immune-suppressive neutrophils. In contrast to the wild-type (WT) neutrophils exhibiting immune-suppressive signatures of CD11b(high)PD-L1(high)CD80(low), IRAK-M-deficient neutrophils are rewired with reduced levels of inhibitory molecules PD-L1 and CD11b, as well as enhanced expression of stimulatory molecules CD80 and CD40. The reprogramming of IRAK-M-deficient neutrophils is mediated by reduced activation of STAT1/3 and enhanced activation of STAT5. As a consequence, IRAK-M-deficient neutrophils demonstrate enhanced capability to promote, instead of suppress, the proliferation and activation of effector T cells both in vitro and in vivo. Functionally, we observed that the transfusion of IRAK-M(-/-) neutrophils can potently render an enhanced anti-tumor immune response in the murine inflammation-induced colorectal cancer model. Collectively, our study defines IRAK-M as an innate suppressor for neutrophil function and reveals IRAK-M as a promising target for rewiring neutrophils in anti-cancer immunotherapy. |
