IRF1 (Interferon Regulatory Factor 1)

Metformin pretreatment significantly enhanced PBMC-mediated cytotoxicity against tumor cells and patient-derived organoids in ex vivo co-culture systems. Our findings establish the SLC5A11-AMPK-PD-L1 axis as a novel mechanism linking metformin to tumor immunity, providing a molecular rationale for combining metformin with checkpoint inhibitors in cancer immunotherapy.

Combining CTX with the next generation MERTK-selective inhibitor UNC2371 (MRX-2843) drives complete remissions in both models, but durable long-term responses occurred selectively in the basal-like subtype model. Suppressive myeloid programing limits effective adaptive immune engagement in TNBC usually resulting in ICB treatment resistance and tumor recurrence. This study identifies a therapeutically actionable myeloid interferon checkpoint in which MERTK inhibition stabilizes CXCL9⁺ monocyte-macrophage programming to promote CD4⁺ T cell dependent immune memory and durable tumor control in basal-like TNBC.

Bone metastasis is an adverse prognostic factor for progression-free survival in lung adenocarcinoma patients treated with third-generation EGFR-TKIs. Bone metastasis lesions exhibit a distinct immunosuppressive tumor microenvironment in EGFR-mutant advanced lung adenocarcinoma, in which upregulation of immune regulatory genes in cancer cells and dysfunction of immune cells may constitute a potential mechanism underlying resistance to third-generation EGFR-TKIs.

Pharmacological inhibition of ZBTB21 with dobutamine disrupts its DNA-binding domain, which triggers pyroptotic inflammation and MHC-I upregulation to synergize with anti-PD-1 therapy. Thus, ZBTB21 represents a druggable nexus coordinating pyroptosis resistance and antigen presentation escape, providing a combinatorial strategy to reinvigorate antitumor immunity.

Its high expression integrates tumor-intrinsic programs (cell cycle, EMT, hypoxia) with tumor-extrinsic immune activation, predicts differential drug sensitivities, and outperforms established biomarkers in forecasting response to immune-checkpoint blockade-particularly in MSI-high disease. These findings nominate IFI30 as a promising diagnostic marker and therapeutic target.

Complementary transcriptomic analysis using a compact four-gene Tα1 Response Index (Tα1-RI: TLR9, TLR2, IRF1, NLRC5) in TCGA-BRCA (n = 1,112) confirmed positive correlations with antigen presentation and cytotoxic programs and enrichment in CD8-like T cells in single-cell datasets. Collectively, these findings demonstrate that Tα1 enhances CD8+ T cell cytotoxicity while alleviating exhaustion, supporting its potential as an adjunct immunomodulator for improving immune surveillance in breast cancer.

Our results also highlighted transcription factors IKZF1, FOSL2, and FOXO1 in the less activated γδ T cells and IRF1, KLF2, and BHLHE40 in the effector γδ T cells that plausibly regulated the differential activation state. Together, our results offer a systems-level view of the signaling and transcriptional programs governing γδ T cell phenotypes in CRC and provide a foundation for γδ T cell-based immunotherapies with enhanced antitumor functions.

These findings suggest that depression may be associated with ovarian cancer progression by remodeling the immune-metabolic microenvironment. This study highlights antidepressant therapy combined with anti-tumor treatment as a potential strategy for ovarian cancer patients with comorbid depression.

Enhanced Prmt7-dependent tumor growth was not observed in immunodeficient mice, implicating Prmt7 in immune evasion. This study underscores the utility of CRISPR screens for high-throughput functional follow-up of GWAS findings and identifies PRMT7 inhibition as a promising therapeutic strategy.

TF activity profiling provides robust stratification for NB, integrating clinical prognostication and immune characterization. This study offers novel insights into TF-driven NB biology, with implications for targeted therapy and immunotherapeutic strategies.

Also, animal study revealed that interference of IRF1 reduced OSCC tumor growth in vivo via decreasing CA9 level. IRF1-mediated transcriptional activation of CA9 could facilitate OSCC progression, providing a novel target for OSCC treatment.