Abstract
Abstract We previously reported that collagen type XI alpha 1 (COL11A1) is upregulated in head and neck squamous cell carcinoma (HNSCC) and contributes to tumor progression. Here we tested the hypothesis that COL11A1 regulates the expression of immune regulatory markers in HNSCC. Xena Browser was used to analyze 520 and 42 cancer free normal head and neck tissue samples for COL11A1 expression. The Cancer Genome Atlas (TCGA) RNASeq data from 522 HNSCC samples was downloaded and sorted by clinical parameters and RNA expression for 20,000 genes. COL11A1 expression was correlated with tumor stage (T) and clinical stage (I-IV). Data was sorted by COL11A1 high and low based on the mean COL11A1 expression level and run through the CIBERSORT analysis tool for prediction of immune cell proportions in the tumor. HNSCC lines with COL11A1 knockdown were assessed for immune regulatory markers at the RNA and protein level. COL11A1 was found to be increased in HNSCC relative to normal tissue (tumor vs. normal p<0.0001). COL11A1 expression is highest in HPV negative HNSCC. Its expression correlates with increased tumor (T1 vs T4 p=0.033) and clinical stage (stage III vs. stage IV p=0.023). CIBERSORT analysis demonstrates COL11A1hi patients have significantly decreased active natural killer (NK) cells (active vs. inactive p=0.0166), CD8+ T cells (CD8 low vs. high p<0.0001) and active dendritic cells (active vs. inactive p=0.0035) suggesting immune modulation. COL11A1 targeted lines in vitro show decreased expression of hla-a, -c and cd274 (PD-L1), suggesting COL11A1 expression modulates immune activation by regulating immune suppressive ligands on the tumor cell. COL11A1 is overexpressed in HNSCC and drives tumor proliferation, migration and invasion. Expression levels correlate with tumor and clinical stage. Bioinformatics tool CIBERSORT, predicts decreased immune cell activity in patients with high COL11A1. Targeting COL11A1 in vitro decreased expression of immune suppressive ligands. These preliminary results indicate COL11A1 may drive immune evasion in HPV negative HNSCC. Targeting COL11A1 may improve patient response to immunotherapeutic targets in HNSCC. Citation Format: Harmony Ivanna Saunders, Levi Arnold, Mary Markiewicz, Sufi M. Thomas. COL11A1: A driver of tumor progression and immune evasion in head and neck squamous cell carcinoma (HNSCC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3844.
Published Version
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