Schutt Charles R, Sun Hua, Pradhan Jaya Sarin, Saenger Yvonne, Ley Jessica, Adkins Douglas, Ingham Matthew, Ding Li, Van Tine Brian A
Division of Medical Oncology, Washington University in St. Louis, St. Louis, MO, USA.
Co-first authors.
Oncotarget. 2021 Mar 16;12(6):534-548. doi: 10.18632/oncotarget.27907.
Head and neck cell squamous-cell carcinomas (HNSCC) are a group of common cancers typically associated with tobacco use and human papilloma virus infection. Up to half of all cases will suffer a recurrence after primary treatment. As such, new therapies are needed, including therapies which promote the anti-tumor immune response. Prior work has characterized changes in the mutation burden between primary and recurrent tumors; however, little work has characterized the changes in neoantigen evolution. We characterized genomic and neoantigen changes between 23 paired primary and recurrent HNSCC tumors. Twenty-three biopsies from patients originally diagnosed with locally advanced disease were identified from the Washington University tumor bank. Whole exosome sequencing, RNA-seq, and immunohistochemistry was performed on the primary and recurrent tumors. Within these tumors, we identified 6 genes which have predicted neoantigens in 4 or more patients. Interestingly, patients with neoantigens in these shared genes had increased CD3+ CD8+ T cell infiltration and duration of survival with disease. Within HNSCC tumors examined here, there are neoantigens in shared genes by a subset of patients. The presence of neoantigens in these shared genes may promote an anti-tumor immune response which controls tumor progression.
头颈部鳞状细胞癌（HNSCC）是一组常见癌症，通常与烟草使用和人乳头瘤病毒感染有关。所有病例中多达一半在初次治疗后会复发。因此，需要新的疗法，包括促进抗肿瘤免疫反应的疗法。先前的研究已经描述了原发性肿瘤和复发性肿瘤之间突变负担的变化；然而，很少有研究描述新抗原进化的变化。我们对23对原发性和复发性HNSCC肿瘤之间的基因组和新抗原变化进行了表征。从华盛顿大学肿瘤库中鉴定出23例最初诊断为局部晚期疾病患者的活检样本。对原发性和复发性肿瘤进行了全外泌体测序、RNA测序和免疫组织化学分析。在这些肿瘤中，我们鉴定出6个基因，在4名或更多患者中具有预测的新抗原。有趣的是，这些共享基因中存在新抗原的患者，其CD3 + CD8 + T细胞浸润增加，疾病生存期延长。在此处检查的HNSCC肿瘤中，一部分患者的共享基因中存在新抗原。这些共享基因中新抗原的存在可能促进抗肿瘤免疫反应，从而控制肿瘤进展。
