OSMR (Oncostatin M Receptor)

Therapeutically, OSMR neutralization with vixarelimab synergized with fluorouracil to overcome chemoresistance and reinstate anti-tumor immunity in GC preclinical models. Our findings establish OSMR as a molecular linchpin connecting intrinsic tumor survival pathways (PI3K/CCNE2) with extrinsic immunosuppressive reprogramming (BMP5/TANs/CD8+T cells), providing a clinically actionable target to overcome treatment resistance in GC.

The framework and nomogram provide valuable insights into the roles of CAFs and key genes in GBM progression and immunity, and extend beyond classification by offering promising avenues for deciphering tumor mutations, mapping immune landscapes, refining drug predictions, and forecasting the efficacy of immunotherapeutic interventions. These findings have the potential to significantly improve personalized treatment strategies and patient outcomes.

A conserved feature across -omics layers, sexes, and conditions was dysregulated Runx1 and neurodegeneration-related pathways, which may indicate cachexia-mediated denervation. Overall, we provide evidence for the role of epigenetics in cachexia progression and severity and a valuable resource to the cachexia research communities.

With the advent of OSMR-targeted therapies, including neutralizing antibodies and signaling inhibitors, OSMR is emerging as a promising therapeutic target for both refractory tumors and inflammatory diseases. This review underscores the clinical significance of the OSM-OSMR signaling pathway in both cancer and inflammatory diseases.

Additionally, high expressions of the 10-NMRGs were noted in the mesenchymal GBM subtype. Collectively, our analysis highlights the potential use of the 10-NMRG signature to stratify the high-risk GBM group with a strong association of immunomodulation and tumour-associated hallmarks that can contribute to the poor survival outcomes.

Importantly, we show that OSMR is required for maintaining CLIC1-mediated ionic balance at the plasma membrane (PM). Our study uncovers a bidirectional crosstalk between OSMR and tmCLIC1 in GB, essential for fueling its malignant growth, and suggest that disrupting the OSMR/tmCLIC1 interaction provides a promising therapeutic avenue for GB treatment.

Finally, silencing OSMR significantly inhibited tumor cell proliferation, invasion, and migration, while markedly reducing the phosphorylation of JAK3 and STAT3, as well as the expression of HIF-1α, VEGFA, and PD-L1. In summary, our findings indicate that OSMR plays a pivotal role in regulating tumor progression and the immune microenvironment in gastric cancer through the JAK/STAT3/HIF-1α signaling pathway.

The oncostatin M receptor (OSMR) has recently emerged as an adverse prognostic factor in acute myeloid leukemia (AML) and several non-hematological malignancies. In this perspective, we discuss how oncostatin M (OSM) and its receptor OSMR regulate tumor cells as well as mesenchymal and endothelial cells, which are key components of hematopoietic stem cell and tumor stem cell niches, and how these mechanisms could explain the poor prognosis associated with high expression of OSM and OSMR in hematological and non-hematological malignancies.

In summary, this study reports the IL-31 structure, revealing a four-α-helical bundle cytokine, and elucidates 2D10-2's neutralizing mechanism by targeting the cIL-31-cOSMRβ interaction. These findings advance our understanding of IL-31 and offer insights for developing IL-31-targeted therapeutics.

Therapeutic targeting of CCL4-CCR5 signaling with maraviroc, an FDA-approved antiviral drug, significantly reduced brain metastasis progression without exerting direct cytotoxic effects on tumor cells. These findings highlight a promising therapeutic strategy that focuses on modulating glial communication within the tumor microenvironment. By disrupting the supportive glial niche rather than targeting tumor cells directly, this represents a distinct and potentially less toxic approach for managing brain metastases.

In all, this study provides the first comprehensive delineation of stage-specific TME dynamics in CC, revealing TGF-β-driven cellular cooperativity as a metastatic switch. The joint framework establishes a potential clinically translatable tool for precision prognosis and therapeutic targeting.

The ROS-associated risk model could accurately predict tumor immunity and progression for GBM patients, acting as an effective predictor of GBM prognosis. The present discovery provided a novel understanding of the diagnosis and treatment of GBM patients.