An Immunogenomic Investigation of Oral Cavity Squamous Cell Carcinoma in Patients Aged 45 Years and Younger

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Abstract

Objectives/Hypothesis: To investigate differences in the immunogenomic landscape among young patients presenting with oral cavity squamous cell carcinoma (OCSCC). Study Design: Retrospective database review. Methods: Normalized messenger mRNA expression data were downloaded from The Cancer Genome Atlas (TCGA) database. OCSCC patients were categorized into young and older age groups with a cutoff of 45 years. Human papillomavirus–positive tumors were excluded. Cell fractions, marker expression, and mutational load were compared between age groups using the Wilcoxon rank sum test. Adjustment for multiple comparisons was performed using the Benjamini-Hochberg method, with a false discovery rate of 0.05. Results: Two hundred forty-five OCSCC tumors were included; 21 (8.6%) were young (37.1 ± 7.5 years) and 224 (91.4%) were older (64.5 ± 10.3 years). There was no significant difference between groups in the fraction of B and T lymphocytes, macrophages, monocytes, natural killers, and dendritic cells. Cytolytic activity score was decreased in young patients (8.33 vs. 18.9, P =.023). Additionally, young patients had significantly lower expression of immunomodulatory markers of immune activation, including PD-1 (PDCD1, P =.003), CTLA4 (P =.025), TIGIT (P =.002), GITR (TNFRSF18, P =.005), OX40 (TNFRSF4, P =.009), LAG-3 (P <.001), and TIM-3 (HAVCR2, P =.002). Young patients had a significantly lower number of single nucleotide variant-derived neoantigens (26.2 vs. 60.6, P <.001). Conclusions: OCSCC patients aged 45 years and younger appear to have an attenuated immune response that may be related to a lower frequency of immunogenic mutations. This may contribute to the pathogenesis of these tumors, and ultimately help inform personalized immune-based therapeutic strategies for young patients with OCSCC. Level of Evidence: NA Laryngoscope, 131:304–311, 2021.

Original languageEnglish (US)
Pages (from-to)304-311
Number of pages8
JournalLaryngoscope
Volume131
Issue number2
DOIs
StatePublished - Feb 2021

Keywords

  • Oral cavity cancer
  • The Cancer Genome Atlas
  • immunogenomics
  • young patients

ASJC Scopus subject areas

  • Otorhinolaryngology

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