LY6E (Lymphocyte Antigen 6 Family Member E)

P1, N=138, Not yet recruiting, EMD Serono Research & Development Institute, Inc.

Finally, we constructed an adverse outcome pathway (AOP) linking 6PPDQ exposure to immune dysregulation and HCC initiation. This multi-omics and in silico study reveals a mechanistic network by which 6PPDQ promotes hepatic carcinogenesis, highlights four candidate biomarkers for early detection, and provides a conceptual AOP framework for future toxicological and therapeutic investigations.

Our findings unveil a novel IFN-γ-nuclear PD-L1/POLR2A-LY6E signaling axis critical for TNBC lung metastasis. This immune-independent mechanism, driven by nuclear PD-L1 transcriptional activity, provides a mechanistic basis for the limited efficacy of anti-PD-L1 antibodies against metastasis and nominates nuclear PD-L1 complexes and LY6E as potential therapeutic targets to overcome metastatic resistance in TNBC.

Our prognosis-related risk model based on DEGs between RCC and LCC may provide better prediction of clinical outcomes for patients with colon cancer.

Furthermore, GSEA and immune cell infiltration analysis revealed distinct molecular and immune profiles between GC and normal tissues. This study provided potential biomarkers and contributed to the theoretical basis for GC prevention and treatment.

Several LY6/uPAR members have emerged as promising clinical targets, with translational strategies encompassing CAR-T cell therapies, antibody-drug conjugates, and lipid raft-modulating agents. This review presents a comprehensive overview of current knowledge, linking the structural, spatial, and functional characteristics of LY6/uPAR proteins to their relevance in health and disease, identifying key unresolved mechanistic questions, and underscoring emerging translational opportunities within the context of precision immunology.

TNFα stimulation, exposure to macrophage-conditioned medium, or coculture with macrophages significantly promoted the self-renewal and proliferation of OSCC cells, but these effects were abolished by LY6E knockdown or NF-κB inhibition. In conclusion, the NF-κB/LY6E axis is a key signaling hub in response to macrophage-OSCC cell interaction in promoting cancer stemness.

The discovery of the SPP1-CD44 ligand-receptor axis not only elucidates a novel inflammatory signaling pathway driving tumor progression, but also provides a potential therapeutic target for disrupting cancer-stromal interactions. Importantly, these biomarkers lay the foundation for developing precision immunotherapies that target the inflammatory-immune axis in GC management.

Furthermore, we confirmed that higher LY6E expression promoted MM cell proliferation and osteoclast differentiation in vitro. Taken together, these findings may illuminate the theoretical foundation for LY6E in MBD formation and identify it as a neoteric therapeutic target for MM.

In conclusion, we created a new prognostic model including 9 inflammation-related genes. This model has produced meaningful results in evaluating patient prognosis, which may help with future therapeutic strategies for patients with uMGMT GBM.

Translation of our findings to the human system showed that high expression of LY6E on tumour cells impaired their physical interaction with NK cells and led to worse prognosis in leukaemia patients. Our results demonstrate that tumour cells are actively edited by NK cells during the equilibrium phase and use different avenues to escape NK cell-mediated eradication.

Our study illuminated that Ly6E-expressing tumor cells facilitated the accumulation of M2 macrophages in TME, which contributes to CD8+ T cell exclusion and provides new insights for improving efficacy of cancer immunotherapy.