IRF8 expression

However, a panel combining IRF8, CD123, and CD20, with at least 1 positive marker was more accurate than any individual marker by receiver operating characteristic curve analysis. Our study provides a rationale for potentially including IRF8 as part of an immunohistochemical panel composed of other currently available markers used to differentiate LEP from SPTCL.

RAS mutations also decrease efficacy of the BCL2 inhibitor venetoclax now widely used in AML, suggesting an anti-apoptotic influence of MAPK signaling...Using GSEA we found that gilteritinib stimulated adaptive interferon/inflammatory gene signatures at 16h drug treatment, but this response was restrained by addition of SEL120...We speculate this latter effect may in part alter an AML cell's differentiation state to sensitize cells to apoptosis, though further study to explore this hypothesis is needed. Our in vitro and in vivo efficacy data further validated combined FLT3i/CDK8i as a promising investigational strategy to pre-empt or overcome MAPK-mediated FLT3 TKI resistance.

Altogether, our results highlight the inflammatory status of the DLBCL microenvironment orchestrated by macrophages. More work is needed to understand the complexity and potential therapeutic implications of inflammasomes in DLBCL.

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.

No abstract available

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.

Furthermore, the TAM-IRF8 signature co-segregated with CTL exhaustion signatures across multiple cancer types. Thus, CTL exhaustion is promoted by TAMs via IRF8.

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.

Conclusions Our studies suggest that eliminating STAT3 checkpoint allows for TLR9-mediated reprogramming of leukemic cells into antigen-presenting cells capable of stimulating adaptive T cell immune responses against AML. Furthermore, these findings support further development of CpG-STAT3 inhibitors as a new bi-functional agent for AML immunotherapy.

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.

IRF8 was negative in all desmoplastic small round cell tumors, Ewing sarcomas, synovial sarcomas, and undifferentiated pleomorphic sarcomas, as well as all epithelial malignancies tested except for 2 triple negative breast cancers that showed subset weak staining. In conclusion, IRF8 is a novel marker helpful in identifying extranodal hematopoietic tumors that can otherwise be difficult to diagnose given the broad differential diagnoses and frequent loss of more common lineage-defining markers.

In this report, we systematically review the precise roles of IL-9, IRF-8, and AP-1 in tumor development, particularly with regard to DLBCL. Finally, the recent progress in IRF-8 and IL-9 research is presented; the possible relationship among IRF-8, IL-9, and AP-1 family members is analyzed; and future research prospects are discussed.

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.

Taken together, these findings demonstrate that IRF8 is a novel marker helpful in identifying extranodal hematopoietic tumors that can otherwise be difficult to diagnose given the broad differential diagnoses and frequent loss of more common lineage-defining markers. Further validation of our observations will be critical in order to integrate IRF8 staining into pathologists’ workflow for diagnosis of myeloid sarcoma and BPDCN.

Thus, GATA2 suppresses TLR signaling in embryonic progenitors. Ongoing s tudies are elucidating the mechanistic interconnections between IRF8- and TLR-dependent inflammatory networks in GATA2 deficiency during embryonic and adult hematopoiesis in cell populations and single cells, relationships between murine and human mechanisms, and the impact of targeted interventions that modulate these mechanisms.

PDX studies are ongoing to validate these results and the effects of SIH on survival. Deconvolution of HSPCs at single cell resolution of other myeloid neoplasms and strategies to mitigate triggers of SIH to prevent the mono-biased state should be explored.

ISIM holds potential as an intralesional therapy to alter the myeloid compartment of TNBC and increase responsiveness to anti-PD-L1 therapy.

Accordingly, ISIM-mediated reduction of PMN-MDSCs was not observed in mice with conditional deletion of IRF8 in myeloid cells. Altogether, these findings suggest that ISIM holds promise as a multimodal intralesional therapy to alter both lymphoid and myeloid compartments of highly aggressive poorly T cell-inflamed, myeloid-enriched tumors resistant to anti-PD-L1 therapy.

In the 12-month therapy period, low IRF4 and IRF8 expression were independently associated with the unfavorable response to HU and high WBC count. Our data indicate that the expression of IRF4 and IRF8 was associated with the MPN phenotype, which may serve as biomarkers for the response to HU in ET.

We propose IRF8 expression as a potent biomarker not only for prognosis, but also for predicting therapy response in ER-negative BC phenotypes. Its expression in neoplastic cells also correlates with CD8 T cell activation and infiltration. Therefore, our results justify new efforts towards understanding mechanisms regulating IRF8 expression and how they can be therapeutically manipulated.

Additionally, many members of the focal adhesion pathway showed reduced expression, providing a putative link between high IRF8 expression and poor prognosis. Thus, this study suggests that IRF8 could serve as a biomarker and potential molecular target in a subset of human AMLs.

We also provide preliminary evidence for the efficacy of IFNα with hormonotherapy in a clinical study. Collectively, this study identifies IRF8 both as a tumor suppressor in PCa pathogenesis and a potential alternative therapeutic option to overcome ENZ resistance.

In summary, we report that macrophage expression of IRF8 is inversely correlated with tumor mass and directly related to survival outcome. These findings support the utilization of IRF8 expression by macrophages to predict patient outcome, which may have important implications for guiding treatment decisions for renal cell carcinoma patients with metastatic disease.

We determined that inhibition of DNMTs with Decitabine (DAC) abolished MDSC accumulation and increased activation of antigen-specific cytotoxic T lymphocytes (CTLs) in tumor-bearing mice...Our data shows that the autocrine IL6 activates the STAT3-DNMT axis to epigenetically silence the TNFα-RIP1 necroptosis pathway to sustain MDSC survival and accumulation in cancer. Targeting the TNFα-RIP1 necroptosis is potentially an effective approach to supress MDSCs to activate tumor-reactive CTLs in the TME.