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Yu, Yang [Author]; Tang, Huiwen [Author]; Francheschi, Debora [Author]; Mujagond, Prabhakar [Author]; Acharya, Aneesha [Author]; Deng, Yupei [Author]; Lethaus, Bernd [Author]; Savkovic, Vuk [Author]; Zimmerer, Rüdiger [Author]; Ziebolz, Dirk [Author]; Li, Simin [Author]; Schmalz, Gerhard [Author]

Immune Checkpoint Gene Expression Profiling Identifies Programmed Cell Death Ligand-1 Centered Immunologic Subtypes of Oral and Squamous Cell Carcinoma With Favorable Survival

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  • Media type: E-Article
  • Title: Immune Checkpoint Gene Expression Profiling Identifies Programmed Cell Death Ligand-1 Centered Immunologic Subtypes of Oral and Squamous Cell Carcinoma With Favorable Survival
  • Contributor: Yu, Yang [Author]; Tang, Huiwen [Author]; Francheschi, Debora [Author]; Mujagond, Prabhakar [Author]; Acharya, Aneesha [Author]; Deng, Yupei [Author]; Lethaus, Bernd [Author]; Savkovic, Vuk [Author]; Zimmerer, Rüdiger [Author]; Ziebolz, Dirk [Author]; Li, Simin [Author]; Schmalz, Gerhard [Author]
  • Published: Lausanne: Frontiers Research Foundation, [2023]
  • Published in: Frontiers in medicine ; 8, (2021)
  • Language: English
  • Keywords: immune subtypes ; oral and squamous cell carcinoma ; PDL1 ; prognosis ; immune checkpoint genes
  • Origination:
  • Footnote:
  • Description: Objective: This study aimed to identify the programmed death ligand-1 (PDL1, alsotermed as CD274) and its positively correlated immune checkpoint genes (ICGs) andto determine the immune subtypes of CD274-centered ICG combinations in oral andsquamous cell carcinoma (OSCC).Materials and Methods: Firstly, the 95 ICGs obtained via literature reviews wereidentified in the Cancer Genome Atlas (TCGA) database in relation to OSCC, and such88 ICG expression profiles were extracted. ICGs positively correlated with CD274 wereutilized for subsequent analysis. The relationship between ICGs positively correlated withCD274 and immunotherapy biomarkers (tumor mutation burden (TMB), and adaptiveimmune resistance pathway genes) was investigated, and the relationships of thesegenes with OSCC clinical features were explored. The prognostic values of CD274 andits positively correlated ICGs and also their associated gene pairs were revealed usingthe survival analysis.Results: Eight ICGs, including CTLA4, ICOS, TNFRSF4, CD27, B- and T-lymphocyteattenuator (BTLA), ADORA2A, CD40LG, and CD28, were found to be positivelycorrelated with CD274. Among the eight ICGs, seven ICGs (CTLA4, ICOS, TNFRSF4,CD27, BTLA, CD40LG, and CD28) were significantly negatively correlated with TMB.The majority of the adaptive immune resistance pathway genes were positivelycorrelated with ICGs positively correlated with CD274. The survival analysis utilizingthe TCGA-OSCC data showed that, although CD274 was not significantly associatedwith overall survival (OS), the majority of ICGs positively correlated with CD274(BTLA, CD27, CTLA4, CD40LG, CD28, ICOS, and TNFRSF4) were significantlycorrelated with OS, whereby their low-expression predicted a favorable prognosis.The survival analysis based on the gene pair subtypes showed that the combinationsubtypes of CD274_low/BTLA_low, CD274_low/CD27_low, CD274_low/CTLA4_low,CD8A_high/BTLA_low, CD8A_high/CD27_low, and CD8A_high/CTLA4_low predictedfavorable OS.Conclusion: The results in this study provide a theoretical basis for prognostic immunesubtyping of OSCC and highlight the importance of developing future immunotherapeuticstrategies for treating oral cancer.
  • Access State: Open Access
  • Rights information: Attribution (CC BY)