We also discovered that PLIN2 expression positively correlated with CSF1R, HAVCR2, IL-10, VEGFR2, LGALS9, PDCD1LG2, TIGIT, and CTLA-4 in HNSCC, indicating that the upregulated PLIN2 level in TME mediated ICI resistance. Here, PLIN2 is linked to head and neck squamous cell carcinoma.