Abstract Inhibitory receptors modulate antigen presentation and myeloid responses within the tumor microenvironment, yet the cross-cancer landscape and clinical significance of LILRB4 remain unclear. By integrating public multi-omics evidence, we delineate its panorama across expression, genetic alterations, DNA methylation, phosphorylation, and immune infiltration, and relate these to patient outcomes. LILRB4 is enriched in immune tissues and in monocytes, macrophages, and dendritic cells, and is upregulated in multiple cancers, with occasional discordance between transcript and protein levels. Its association with survival is cancer-type dependent—protective in cervical cancer, skin cutaneous melanoma, and uterine corpus endometrial carcinoma, but indicating higher risk in lower-grade glioma and in recurrence-related metrics of prostate adenocarcinoma. Genetic alterations are dominated by amplification and missense mutations and cluster within immunoglobulin domains, including a P184 hotspot, but carriers of alterations do not exhibit consistent survival differences. LILRB4 expression positively correlates with tumor mutational burden, microsatellite instability, and homologous recombination deficiency in several cancers. In lower-grade glioma, hypermethylation at a key promoter-proximal CpG site associates with longer survival, and multiple cancers display site- and cancer-specific phosphorylation remodeling. LILRB4 correlates strongly with macrophage infiltration, and co-expression and interaction networks are enriched for antigen processing and presentation, pointing to HLA-DRA. Collectively, these data position LILRB4 as a context-dependent marker of the myeloid and antigen-presentation axis in the tumor microenvironment and provide a basis for stratification and immunoregulatory strategies.
Li et al. (Fri,) studied this question.