LILRB1 immune cell infiltration identifies immunosuppressive microenvironment and dismal outcomes of patients with ovarian cancer.

OBJECTIVE

Immune checkpoint inhibitors are commonly used in various types of cancer, but their efficacy in ovarian cancer (OC) is limited. Thus, identifying novel immune-related therapeutic targets is crucial. Leukocyte immunoglobulin-like receptor subfamily B1 (LILRB1), a key receptor of human leukocyte antigen G (HLA-G), is involved in immune tolerance, but its role in tumor immunity remains unclear.

METHODS

In this study, immunofluorescence was used to identify the location of LILRB1 in OC. The effect of LILRB1 expression on clinical outcomes in 217 patients with OC was analyzed retrospectively. A total of 585 patients with OC from the TCGA database were included to explore the relationship between LILRB1 and tumor microenvironment characteristics.

RESULTS

LILRB1 was found to be expressed in tumor cells (TCs) and immune cells (ICs). High LILRB1 ICs, but not LILRB1 TCs, were associated with advanced FIGO stage, shorter survival outcomes, and worse adjuvant chemotherapy responses in OC patients. LILRB1 expression was also associated with high M2 macrophage infiltration, reduced activation of dendritic cells, and dysfunction of CD8 T cells, suggesting an immunosuppressive phenotype. The combination of LILRB1 ICs and CD8 T cell levels could be used to distinguish patients with different clinical survival results. Moreover, LILRB1 ICs infiltration with CD8 T cells absence indicated inferior responsiveness to anti-PD-1/PD-L1 therapy.

CONCLUSIONS

Tumor-infiltrating LILRB1 ICs could be applied as an independent clinical prognosticator and a predictive biomarker for therapy responsiveness to OC. Further studies targeting the LILRB1 pathway should be conducted in the future.