IRF8 overexpression

Using a xenograft mouse model, we discovered the antiproliferative effect of losing IRF8 in vivo. In conclusion, this study found that IRF8 may play a prognostic factor and therapeutic target in AML.

Targeting the FTO-IRF8 axis is used as a proof of concept therapy; inhibition of FTO's demethylase activity drastically alleviates the proliferation of leukemic cells and prolongs the survival of T-ALL mice by restoring IRF8 expression. This study elucidates the pathogenesis of T-ALL from the perspective of epitranscriptomics and provides new insight into the genetic mechanisms and targeted therapy of T-ALL.

PD-L1 was expressed in human osteosarcoma tissues, and its expression was moderately correlated with that of ICSBP in osteosarcoma patients. ICSBP regulates PD-L1 expression in osteosarcoma cells, and PD-L1 knockdown combined with doxorubicin treatment could represent a strategy for controlling osteosarcoma expressing ICSBP.

In addition to forming a circuit, MEF2D and IRF8 can also separately regulate gene expression, and dual perturbation of these two TFs leads to a more robust inhibition of AML proliferation. Collectively, our results revealed a TF circuit essential for AML survival.

Immunohistochemical analysis in a large cohort of primary DLBCL (n=206) revealed a significant correlation of IRF8 expression with detectable CD37 levels. Together, this study provides new insight into the molecular mechanisms underlying differential CD37 expression in human DLBCL, and reveals IRF8 as transcriptional regulator of CD37 in B-cell lymphoma.

Importantly, adeno-associated virus 8-mediated hepatic IRF8 rescue significantly suppressed HCC progression and enhanced the response to anti-PD-1 therapy. In This work identified IRF8 as an important prognostic biomarker in HCC patients which predicted the response and sensitivity to anti-PD-1 therapy and uncovered it as a new therapeutic target for enhancing the efficacy of immune therapy.