Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, Baltimore, Maryland, U.S.A.
Bloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, Baltimore, Maryland, U.S.A.
Laryngoscope. 2021 Feb;131(2):304-311. doi: 10.1002/lary.28674. Epub 2020 Apr 16.
OBJECTIVES/HYPOTHESIS: To investigate differences in the immunogenomic landscape among young patients presenting with oral cavity squamous cell carcinoma (OCSCC).
Retrospective database review.
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.
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).
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.
NA Laryngoscope, 131:304-311, 2021.
目的/假设：研究年轻口腔鳞状细胞癌（OCSCC）患者的免疫基因组图谱差异。
回顾性数据库研究。
从癌症基因组图谱（TCGA）数据库下载标准化信使 mRNA 表达数据。将 OCSCC 患者分为年轻和老年组，分界点为 45 岁。排除人乳头瘤病毒阳性肿瘤。使用 Wilcoxon 秩和检验比较年龄组之间的细胞分数、标志物表达和突变负荷。使用 Benjamini-Hochberg 方法进行多重比较调整，假发现率为 0.05。
纳入 245 例 OCSCC 肿瘤，其中 21 例（8.6%）为年轻（37.1±7.5 岁），224 例（91.4%）为老年（64.5±10.3 岁）。两组间 B 和 T 淋巴细胞、巨噬细胞、单核细胞、自然杀伤细胞和树突状细胞的比例无显著差异。年轻患者的细胞毒性活性评分降低（8.33 与 18.9，P=.023）。此外，年轻患者免疫激活的免疫调节标志物表达水平显著降低，包括 PD-1（PDCD1，P=.003）、CTLA4（P=.025）、TIGIT（P=.002）、GITR（TNFRSF18，P=.005）、OX40（TNFRSF4，P=.009）、LAG-3（P < .001）和 TIM-3（HAVCR2，P=.002）。年轻患者的单核苷酸变异衍生的新抗原数量明显减少（26.2 与 60.6，P < .001）。
年龄在 45 岁及以下的 OCSCC 患者似乎存在减弱的免疫反应，这可能与免疫原性突变的频率较低有关。这可能有助于这些肿瘤的发病机制，并最终有助于为年轻的 OCSCC 患者提供个性化的免疫治疗策略。
无 喉科学，131：304-311，2021 年。
