WCLC 2025 - Posters & ePosters-P2.06.33 Prognostic Significance and Therapeutic Potential of LILRB4 in Mdsc-Mediated Immunosuppression in NSCLC

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This study investigates the prognostic significance and therapeutic potential of LILRB4, an immunoregulatory receptor, in non-small cell lung cancer (NSCLC), focusing on its role in myeloid-derived suppressor cell (MDSC)-mediated immunosuppression. LILRB4 is known to facilitate immune evasion, and prior mouse studies demonstrated its role in promoting MDSC-mediated tumor metastasis. However, its clinical relevance in human NSCLC was unclear.<br /><br />The researchers evaluated LILRB4 expression in tumor-infiltrating cells from NSCLC specimens, examining associations with clinicopathological features and patient prognosis. Immunohistochemical analysis revealed variable LILRB4 expression among NSCLC samples, with LILRB4 co-expressed on CD33+ and CD14+ MDSCs within the tumor stroma. Higher LILRB4 expression correlated significantly with factors such as sex, smoking history, cancer histology, SUVmax (tumor metabolic activity), and vascular invasion.<br /><br />Importantly, patients with high LILRB4 expression exhibited significantly shorter overall survival (OS) and relapse-free survival (RFS) compared to those with low expression. Multivariate Cox regression confirmed LILRB4 as an independent prognostic marker for poor OS and RFS. Functional in vitro assays demonstrated that blocking LILRB4 reduced cancer cell migration in several human lung cancer cell lines cocultured with CD33+ MDSCs, suggesting a role in promoting tumor progression.<br /><br />Therapeutically, LILRB4 blockade may restore anti-tumor immunity and enhance immune checkpoint inhibitor efficacy, supported by preclinical evidence of synergy between anti-LILRB4 and anti-PD-1 therapies in mouse models. An ongoing clinical phase 1 trial is testing an anti-LILRB4 antibody in combination with pembrolizumab.<br /><br />Limitations include limited patient stages (mostly resected NSCLC) and LILRB4 expression on other immune cells such as B cells and regulatory T cells, which may complicate therapeutic targeting.<br /><br />In conclusion, high LILRB4 expression on tumor-infiltrating MDSCs is linked to poor prognosis and tumor recurrence in NSCLC. Targeting LILRB4 represents a promising strategy to counteract MDSC-mediated immunosuppression and improve NSCLC treatment outcomes.

Asset Subtitle

Sakiko Kumata

Meta Tag

Speaker Sakiko Kumata

Topic Pathology and Biomarkers

Keywords

LILRB4

non-small cell lung cancer

NSCLC

myeloid-derived suppressor cells

MDSCs

immunosuppression

prognostic marker

tumor metastasis

immune checkpoint inhibitors

anti-LILRB4 therapy