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

Christopher A Maroun; Gangcai Zhu; Carole Fakhry; Christine G Gourin; Tanguy Y Seiwert; Peter S Vosler; Marietta Tan; Wayne Koch; David W Eisele; Drew M Pardoll; Rajarsi Mandal

doi:10.1002/lary.28674

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

Laryngoscope. 2021 Feb;131(2):304-311. doi: 10.1002/lary.28674. Epub 2020 Apr 16.

Authors

Christopher A Maroun^{1

2}, Gangcai Zhu^{1

2}, Carole Fakhry^{1

2}, Christine G Gourin¹, Tanguy Y Seiwert^{2

3}, Peter S Vosler¹, Marietta Tan¹, Wayne Koch¹, David W Eisele¹, Drew M Pardoll^{2

3}, Rajarsi Mandal^{1

2}

Affiliations

¹ Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, Baltimore, Maryland, U.S.A.
² Bloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, Baltimore, Maryland, U.S.A.
³ Department of Oncology, Johns Hopkins University, Baltimore, Maryland, U.S.A.

PMID: 32297993
DOI: 10.1002/lary.28674

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.

Keywords: Oral cavity cancer; The Cancer Genome Atlas; immunogenomics; young patients.

Publication types

Evaluation Study

MeSH terms

Adult
Age Factors*
Aged
Carcinoma, Squamous Cell / genetics*
Carcinoma, Squamous Cell / immunology
Databases, Factual
Female
Humans
Immunogenetic Phenomena / genetics*
Immunologic Factors / blood*
Male
Middle Aged
Mouth Neoplasms / genetics*
Mouth Neoplasms / immunology
Polymorphism, Single Nucleotide
Retrospective Studies

Substances

Immunologic Factors