Purpose: We systematically analyzed
HNSCC-infiltrating T lymphocytes lncRNAs (HILTlncRNAs) to assess their predictive value for the survival outcome and
immunotherapy response of patients with anti-programmed death-1 (PD-1)
therapy and to evaluate their predictive power to chemotherapeutic agents. Methods:
HNSCC transcriptome and clinical information was obtained from The
Cancer Genome Atlas (TCGA) database. Immunocell microarray data were obtained from the Gene Expression Omnibus (GEO) database. T-cell-specific lncRNAs were identified by differential expression analysis. Prognostic paired HILTlncRNAs (PHILTlncRNAs) were filtered and modeled by univariate cox, lasso and multivariate cox regression analysis. To construct
lncRNA-
miRNA-
mRNA competitive endogenous RNA (
ceRNA) regulatory networks, differentially expressed mRNAs in
HNSCC patients were incorporated,
microRNAs and differentially expressed mRNAs interacting with T-cell-specific lncRNAs were filtered out based on miRcode, miRDB, miRTarBase, and TargetScan databases. Results: 75 T-cell-specific lncRNAs and 9 prognostic PHILTlncRNAs were identified. Low-risk
HNSCC patients had a better prognosis and significant immune cell infiltration, driving the immune response. Differential expression of
RNA-binding proteins (RBPs), PD-1 and
programmed cell death 1 ligand 1 (PD-L1) was demonstrated in the high and low risk groups of
HNSCC patients. In the high risk group, high expression of PD-1 improved patient prognosis, whereas the opposite was observed in the low-risk group. The promoter methylation levels of two RBPs (DNMT1 and ZC3H12D) were decreased in
HNSCC patients compared with normal samples, their expression levels were positively correlated with PD-1 and PD-L1 levels and T-cell infiltration. Finally, we screened the sensitivity of
HNSCC patients to chemotherapeutic agents and found it differed between high and low risk groups. Conclusion: HILTlncRNAs provided a theoretical basis for immune targeted
therapy and drug development.