TNFSF4 (TNF Superfamily Member 4)

TNFSF4 was a candidate driver and a prognostic biomarker, promoting HCC progression by activating the PI3K/Akt signaling pathway. Furthermore, fluspirilene may have applications as a repositioned drug for HCC with high TNFSF4 expression.

OX40L protein expression is a heterogeneous but prominent feature of the melanoma microenvironment, with cell type-specific expression patterns that include regulatory T cells. An exploratory association was seen between myeloid OX40L expression and clinical outcome, warranting further investigation.

By conducting transcriptomic identity, lineage-traced ontogeny, surface marker expression and functional studies, we identified and characterized this DC population. Our data demonstrated that TSLP acts on transitional dendritic cell-derived DC2 to promote GATA3+ eTreg cells, thus uncovering a previously unrecognized tolerogenic axis in promoting immunosuppression, which is likely conserved in humans, across contexts of inflammation and cancer.

These results demonstrate the utility of a modular NP design for systematic screening of signal 2/3 delivery to melanoma in vivo and highlight the benefit of in-depth profiling via spatial proteomics to evaluate local antitumor immune responses. The results provide insight into the mechanisms underpinning this therapeutic reprogramming strategy, emphasizing the relationship between signal 2/3 NPs and their ability to drive signal 1 for productive antitumor responses in vivo.

Despite higher objective response rates with the addition of PD-1, radiotherapy, or chemotherapy, grade 3-4 immune-related adverse events were associated with higher rates. In the future, novel OX40 agonists with high affinity and selective activation in the tumor microenvironment should be developed or incorporated into the framework of combined immunotherapy as an adjuvant strategy to achieve a balance between efficacy and safety.

Mechanistically, ssRNAs expressing co-stimulatory molecules promoted immune cell infiltration into the tumor site and increased the cytotoxic CD8+ T cells while reducing regulatory T cells (Tregs) in secondary lymphoid organs. These findings suggest that IRES-based ssRNAs expressing co-stimulatory molecules represent a promising platform for the development of effective cancer immunotherapies.

This study demonstrates the potential of a triplet RNA platform-comprising immunostimulatory RNA, mRNA, and siRNA, delivered via a single versatile LNP. The data support development of pIpC-LNPs as potent intratumoral therapeutics and highlight several potential synergistic targets.

The IL-2/OX40L adenoviral vector effectively activated TILs, which subsequently induced prominent apoptotic responses in primary GC tumor cells. Our study demonstrates that a costimulatory immunotherapy strategy combining IL-2 and OX40L significantly enhances antitumor responses in PBMCs and TILs from GC patients, showing strong therapeutic potential as a complementary approach for the treatment of GC.

Mechanistically, decreased oar-miR-125b expression relieves its repression of TNFSF4, leading to NF-κB pathway activation and blood-brain barrier disruption. Collectively, our results demonstrate that oar-miR-125b serves as a key anti-inflammatory regulator in bacterial meningitis by targeting TNFSF4 and constraining NF-κB signaling, highlighting its potential as a therapeutic target for attenuating neuroinflammation in meningitis.

In this study, we identified several hot spot residues from the OX40 cysteine-rich domains (CRDs) 1 to 3 by alanine scanning. Kinetic and thermodynamic analysis combined with molecular dynamics simulations highlighted the characteristics of a hot spot from CRD3 due to its indirect influence on those from CRD1 and CRD2, providing insights into the interaction mechanism and a strategy for drug discovery targeting this interaction.

Depleting CD4+ T-cells, or blocking lymphocyte egress from the lymph nodes with FTY720, rescues tumor growth in mice with conditional deletion of Dnmt1 in ECs (Dnmt1iECKO) and dramatically shortens overall survival, whereas NK cells are dispensable...Finally, immune checkpoint blockade (ICB) administered to Dnmt1iECKO mice with experimental melanoma lung metastasis reduces tumor burden, with some mice showing tumor eradication. Our findings identify endothelial Dnmt1 as a key regulator of vascular-mediated anti-tumor immunity, providing a rationale for integrating epigenetic modulation of the vasculature with cancer immunotherapy regimens.

This study identified three LUAD subtypes with distinct immune characteristics and constructed a seven-gene prognostic model. This model correlates with immune checkpoint and chemotherapy sensitivity, providing new targets and strategies for clinical diagnosis and treatment.