Abstract
Background
Leukocyte immunoglobulin (Ig)-like receptor Bs (LILRBs), a family of type I transmembrane glycoproteins, are known to inhibit immune activation.
Methods
We comprehensively evaluated the transcriptional levels and prognostic significances of LILRB members in a broad spectrum of cancer types, focusing on its role in AML. In addition, we systematically characterized the genomic and immune landscape in AML patients with altered LILRBs expression.
Results
Here, we show that LILRBs were significantly dysregulated in a number of cancers, especially in acute myeloid leukemia (AML). Clinically, high expression of LILRB1-LILRB4 predicted poor survival in six independent AML cohorts. Genetically, LILRB1 was associated with more mutational events than other LILRB members, and multiple genes involving in immune activation were deleted in LILRB1-high patients. Epigenetically, LILRB4 was significantly hypomethylated and marked by MLL-associated histone modifications in AML. Immunologically, LILRBs were positively associated with monocytic cells including M2 macrophages, but were negatively associated with tumor-suppressive CD8 T cells.
Conclusions
Our findings reveal critical immunological and clinical implications of LILRBs in AML, and indicate that LILRBs may represent promising targets for immunotherapy of AML.