A pan-cancer landscape of LILRB4 identifies it as a context-dependent marker of the myeloid and antigen-presentation axis

Inhibitory receptors modulate antigen presentation and myeloid responses within the tumor microenvironment, yet the cross-cancer landscape and clinical significance of LILRB4 remain incompletely defined. By integrating public multi-omics resources, we systematically profiled LILRB4 across expression, genetic alterations, DNA methylation, phosphorylation, and immune infiltration, and examined their associations with clinical 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 carcinosarcoma, but associated with higher risk in lower-grade glioma and recurrence-related metrics of prostate adenocarcinoma. Genetic alterations are dominated by amplification and missense mutations clustering within immunoglobulin domains, including a P184 hotspot, yet carriers do not show 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 promoter-proximal CpG site associates with longer survival, and multiple cancers display site- and cancer-specific phosphorylation differences. LILRB4 correlates strongly with macrophage infiltration, and co-expression and interaction analyses converge on antigen processing and presentation pathways, with HLA-DRA emerging as a shared node. Collectively, these findings support LILRB4 as a context-dependent marker of the myeloid and antigen-presentation axis in the tumor microenvironment and provide an integrated reference framework that warrants further functional validation.