IRF2 (Interferon Regulatory Factor 2)

The relative levels of E4F1 and IRF2 differ by cell-type and play a role in mediating transcriptional activity in a cell-type specific manner. Our results indicate that the top credible causal set variant rs3769823 likely influences expression of CASP8 and FLACC1 in a cell-type specific manner and may be a relevant functional variant for multiple cancers associated with this locus.

In vitro, IRF2 knockdown in HL-1 murine cardiomyocytes via siRNA upregulated PD-L1 expression, suppressed TAP2/ERAP1 levels and attenuated T-cell proliferation while promoting apoptosis in co-culture systems. We elucidate the principal mechanism underlying IRF2-mediated allograft immune evasion, thereby identifying its targeted modulation as an innovative therapeutic approach to prevent early acute rejection and diminish long-term reliance on immunosuppressive therapy in transplantation.

Finally, IRF1 expression, transcription rate, and enhancer activity induced by IL-1β, or TNFα, were relatively unaffected by glucocorticoid. IRF1-dependent gene expression may therefore show insensitivity to glucocorticoid and could contribute to glucocorticoid-resistance in diseases that include severe asthma.

Mechanistically, IRF2-mediated Oasl2 downregulation activates the cGAS-STING pathway, augmenting DNA damage signaling cascades. In vivo validation demonstrates significant tumor suppression and prolonged survival without observable toxicity, establishing LipNaB@Sor as a translatable strategy to overcome therapy resistance in immunologically unresponsive CRC.

Experimental validation confirmed significant increased expressions of PECAM1, IFI16, AIM2, and MPEG1 in the salivary glands from both NOD mice and pSS patients. PECAM1, IFI16, AIM2, and MPEG1 were identified as PRG signatures and potential biomarkers in pSS, providing novel insights into pSS pathogenesis.

In summary, our study demonstrates that IRF2BPL is downregulated in osteosarcoma and serves as a prognostic marker. Functional assays confirmed that IRF2BPL suppresses tumor cell proliferation, migration, and invasion, while its silencing exerts the opposite effect. Mechanistically, IRF2BPL regulates the FOSL2/PI3K/AKT/mTOR axis through ubiquitin-mediated degradation, highlighting its potential as a therapeutic target in osteosarcoma.

Furthermore, we found associations between PRGRS and tumor immune response. Our study highlights novel pyroptosis-related gene signatures that may be utilized for early screening and prognosis prediction in UCEC patients, offering potential targets for future research and guidance for personalized anticancer therapies.

While the development of venetoclax with azacitidine (ven/aza) has improved AML therapy, drug resistance remains a major challenge. Inhibition of ACSL1 functionally impaired ven/aza-resistant LSC through a depletion of long-chain acyl-carnitine metabolites and FAO. Collectively, these data provide evidence for a previously undescribed mechanism by which MCL1 mediates IRF2BP2 cytoplasmic sequestration and consequent de-repression of ACSL1 , thereby promoting ven/aza-resistance in AML.

In fact, expression of an LA-like gene signature prognosticates survival for patients receiving atezolizumab plus bevacizumab in the IMbrave150 phase III trial and inversely correlates with CTNNB1-mutatational status in this patient cohort. In conclusion, LNP-CTNNB1 is efficacious as monotherapy and in combination with ICI in CTNNB1-mutated HCCs through impacting tumor cell-intrinsic signaling and remodeling global immune surveillance, providing rationale for clinical investigations.

These findings highlight OAS3 as a critical player in AML pathogenesis, functioning through the JAK-STAT pathway activation under the transcriptional control of IRF2. The study suggests that OAS3 could serve as a valuable prognostic marker and therapeutic target, offering a promising avenue to improve AML treatment outcomes.

Future research must prioritize the refinement of isolation and production protocols, the development of precise delivery strategies, and the execution of comprehensive safety evaluations to unlock their full clinical potential in treating hematological disorders and beyond. This review integrates recent advancements to provide a clearer understanding of their multifaceted contributions and highlights the critical gaps that remain.

Overall, this work represents the first systematic analysis of how the absence of individual APPM components, knocked out in a single cell line under controlled conditions, affects the peptidome. This approach could facilitate the creation of predictive tools capable of prioritizing HLA-bound peptides likely to be presented when presentation defects occur, such as in cancer and viral infections.