TNFRSF1A (TNF Receptor Superfamily Member 1A)

By modulating the valency of the TNFR1-directed sdAb, killing capacities as well as caspase activities of HER2-targeted ICMs were significantly augmented, eventually resulting in enhanced cell death induction when compared with TNF. Moreover, HER2-targeted TNFR1 ICMs also displayed a beneficial, i.e., substantially reduced profile in inducing unconditional pro-inflammatory cytokine release from peripheral blood mononuclear cells (PBMCs).

The TNFRSF1A (-135 T>C) polymorphism influences both toxicity and response in HNSCC, with the C allele predisposing to mucositis and the TT genotype predicting favorable outcomes. It represents a potential biomarker for personalized radiotherapy, meriting validation in larger cohorts.

Complementary analysis of cerebrospinal fluid from individuals with ischemic stroke revealed sex-specific increases in soluble TNFR1, elevated across stroke severities in females. Together, these findings identify TNFR1 as a sex-dependent modulator of neuroinflammatory injury and synaptic function, highlighting its potential as a cell-type-specific therapeutic target in ischemic brain injury.

We additionally report that the translation of other immune receptor messenger RNAs, including TLR4, IFNAR1, and IFNGR2, is also controlled by uORFs. Thus, regulation of TNFR1 levels and possibly of other immune receptors emerges as a mechanism safeguarding against excessive immune responses and tissue damage.

Moreover, fimepinostat downregulated cytokine and chemokine secretion increased by merlin loss in schwannoma cells. Fimepinostat is a promising new drug intervention for NF2-SWN patients with the potential to promote tumor regression.

Overall, this study primarily provides descriptive and hypothesis-generating evidence of differential inflammatory patterns across colorectal neoplasia, with PDGF-AA emerging as the most robust signal in this exploratory dataset. These findings do not support immediate diagnostic application and require validation in larger, prospectively recruited cohorts.

Together, these findings support that increased NF-κB induces cytokine mRNA expression in schizophrenia midbrain via multiple upstream activators and cell types. The widespread increase in multiple NF-κB transcripts highlights both redundant activation mechanisms and a putative attempt to control NF-κB activation.

We developed a 5-factor SASP model that demonstrated superior predictive performance for OS compared to chronological age, R-ISS stage, and clinical frailty, and TNF-RI alone (5-year OS AUC: 0.90). These findings highlight the association between senescence biomarkers and frailty and OS, and support further investigation of SASP factors as objective frailty biomarkers in MM.

These immune alterations were observed across multiple clinical subgroups, though with distinct patterns, such as enrichment of TNFR2+ T cells in LN+ patients and higher TNFR2+ B-cell frequencies in LN- patients. Elevated TNFR2 expression on peripheral lymphocytes, despite overall lymphocyte depletion, underscores its potential as a biomarker and immunomodulatory target in breast cancer progression.

Combinatorial gene KOs in CAFs reveals a circuit where these Col18a1hi CAFs reshape the TME by recruiting Siglec-Fhi neutrophils via Cxcl5 expression, and where this Col18a1hi CAF cell state is dependent on TNFR1 and canonical Wnt signaling. Together, a fast, affordable, and modular engineering method is demonstrated, allowing discovery of modified fibroblast identities and local intercellular relationships in the TME.

Compared to wild-type mice, MINDY2-deficient mice exhibit more severe hypothermia, mortality, and intestinal damage after TNF-α challenge. Collectively, our work reveals that MINDY2 is a checkpoint in RIPK1-dependent cell death, and that its deficiency exacerbates TNF-mediated tissue damage in vivo.

Intracranial orthotopic xenograft experiments validate the function of NANP in vivo. Here, we identify NANP as a radiosensitizing target dependent on TNFR1 sialylation and mesenchymal shift, providing a basis for developing RT sensitizers for GBM.