LILRB1 Is a Prognostic-Related Biomarker Correlated With Immune Infiltration in Head-Neck Squamous Cell Carcinoma

Conventional treatment strategies and immunotherapy yield low response rates in head and neck squamous cell carcinoma (HNSCC). This study aimed to explore the potential of immunosuppressive receptor leukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1) for developing effective immunotherapies for HNSCC.

Clinical data collection and analysis were determined using Tumor Immunity Estimation Resource Database (TIMER) and Cancer Treatment Response gene signature DataBase (CTR-DB). Immunohistochemistry was used to detect protein level in fresh breast cancer tissues. RNA sequencing was employed to screen the downstream signaling pathway in WBP2-overexpressed cells. Tumor xenograft model and Flow Cytometry were performed to monitor tumor growth and cell apoptosis, respectively.

In this study, high expression of LILRB1 in HNSCC tissues was observed compared to normal tissues. HNSCC patients with high LILRB1 expression exhibited a better prognosis, which was influenced by tumor mutation burden. Functional network analysis revealed a positive association between LILRB1 and chemokine signaling pathways. Copy number variation of LILRB1 was positively correlated with the infiltration of CD8+ T cells and M1 macrophages. The prognostic effect of LILRB1 depends on CD8+ T-cell abundance, especially in HNSCC with a low neoantigen load. High LILRB1 expression was associated with a higher immune score, indicating favorable outcomes in HNSCC patients receiving immunotherapy. Notably, LILRB1 was specifically expressed in SPP1-ACP5+ macrophages; in these cells, high LILRB1 might reduce the proportion of cancer cells via the SPP1-CD44 axis, and subsequently regulate CD8+ T cell enrichment through the C-X-C motif chemokine 13 (CXCL13)-CXCR5 axis.

Collectively, high LILRB1 expression in HNSCC was accompanied by the infiltration of various immune effector cells. LILRB1 may shape the tumor microenvironment of HNSCC, mediating the interactions between cancer cells and macrophages, as well as between cancer cells and CD8+ T cells, via the SPP1-CD44 and CXCL13-CXCR5 axes. Our findings illustrate that LILRB1 serves as a prognostic-related biomarker associated with immune infiltration in HNSCC.