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.<h4>Conclusion</h4>Collectively, high LILRB1 expression in HNSCC was accompanied by the infiltration of various immune effector cells. Here, CD44 is linked to head and neck squamous cell carcinoma.