Tumor-Infiltrating Immune-Related Long Non-Coding RNAs Indicate Prognoses and Response to PD-1 Blockade in Head and Neck Squamous Cell Carcinoma

Abstract

Long non-coding RNAs (lncRNAs) in immune cells play critical roles in tumor cell–immune cell interactions. This study aimed to characterize the landscape of tumor-infiltrating immune-related lncRNAs (Ti-lncRNAs) and reveal their correlations with prognoses and immunotherapy response in head and neck squamous cell carcinoma (HNSCC). We developed a computational model to identify Ti-lncRNAs in HNSCC and analyzed their associations with clinicopathological features, molecular alterations, and immunotherapy response. A signature of nine Ti-lncRNAs demonstrated an independent prognostic factor for both overall survival and disease-free survival among the cohorts from Fudan University Shanghai Cancer Center, The Cancer Genome Atlas, GSE41613, and GSE42743. The Ti-lncRNA signature scores in immune cells showed significant associations with TP53 mutation, CDKN2A mutation, and hypoxia. Inferior signature scores were enriched in patients with high levels of PDCD1 and CTLA4 and high expanded immune gene signature (IGS) scores, who displayed good response to PD-1 blockade in HNSCC. Consistently, superior clinical response emerged in melanoma patients with low signature scores undergoing anti-PD-1 therapy. Moreover, the Ti-lncRNA signature was a prognostic factor independent of PDCD1, CTLA4, and the expanded IGS score. In conclusion, tumor-infiltrating immune profiling identified a prognostic Ti-lncRNA signature indicative of clinical response to PD-1 blockade in HNSCC.

Predicting prognosis and immunotherapy response among colorectal cancer patients based on a tumor immune microenvironment-related lncRNA signature

“…Having the power to rewrite the regulation network in the tumor-infiltrating immune cells and the TIME ( Uthaya Kumar and Williams, 2020 ; Wells et al, 2020 ), lncRNAs also take part in controlling the immune surveillance, drug resistance and the efficacy of immunotherapy ( Pi et al, 2021 ). Many studies have shown that immune-related lncRNAs were capable of predicting the response for immune checkpoint inhibitor therapy ( Jiang et al, 2020 ; Sun et al, 2020 ; Ma et al, 2021 ; Xu et al, 2021 ; Zhou et al, 2021 ). Consistent with the reported findings, the CRC TRLs signature provided us with immunotherapy treatment indications, showing that patients of the high-risk group were associated with higher expression of cellular receptors targeted by immune checkpoint inhibitor therapy and favorable response towards immunotherapy, which is of great help to stratify CRC patients for immunotherapy ( Bateman, 2021 ).…”

The role of LncRNAs in tumor immunotherapy

“…Ben Ma et al developed computational models to identify tumor-infiltrating immune-related lncRNAs (Ti-lncRNAs) in HNSCC and analyzed their relationship with clinicopathological features, molecular changes, and immunotherapy response. They demonstrated Ti-lncRNAs signature was an independent prognostic predictor in HNSCC [ 84 ]. PD-1 expression is associated with methylation in HNSCC.…”

The role of lncRNAs in the tumor microenvironment and immunotherapy of melanoma

“…As a monoclonal therapy, PD-1 has been used in the treatment of multiple tumors, including melanoma, and can predict the survival of patients. Recent studies have described the characteristics of tumor infiltrating immune-related lncRNAs (Ti-lncRNAs) and have found a better efficacy of anti-PD-1 treatment in melanoma patients with a low Ti-lncRNA score ( 116 ). WGCNA indicated that 15 lncRNAs, such as NARF-AS1 and LINC01126, were identified to predict the prognosis of melanoma patients treated with anti-PD-1 ( 117 ).…”