Abstract
Simple SummaryIn this review, we discuss the roles of cancer/testis antigens in the germline and their contributions to oncogenic cellular processes. Specifically, we focus on their clinical utility in head and neck squamous cell carcinoma and consider how cancer/testis antigens differentially expressed in HPV-positive HNSCC might contribute mechanistically to the genesis and clinical characteristics of these cancers.Cancer/testis (CT) antigens exhibit selective expression predominantly in immunoprivileged tissues in non-pathological contexts but are aberrantly expressed in diverse cancers. Due to their expression pattern, they have historically been attractive targets for immunotherapies. A growing number of studies implicate CT antigens in almost all hallmarks of cancer, suggesting that they may act as cancer drivers. CT antigens are expressed in head and neck squamous cell carcinomas. However, their role in the pathogenesis of these cancers remains poorly studied. Given that CT antigens hold intriguing potential as therapeutic targets and as biomarkers for prognosis and that they can provide novel insights into oncogenic mechanisms, their further study in the context of head and squamous cell carcinoma is warranted.
Highlights
Head and neck squamous cell carcinoma (HNSCC), comprising cancers derived from the oral cavity, nasopharynx, oropharynx, hypopharynx, and larynx, accounted for 796,577 new cancer cases and 387,117 cancer-related deaths in 2020 worldwide [1,2]
High HORMAD1 overexpression is associated with increased tumor burden and neoantigen counts in breast invasive carcinoma, head and neck squamous cell carcinoma, lung adenocarcinoma, and thymoma in an analysis of genomes deposited in The Cancer Genome Atlas (TCGA)
Many of them are expressed in HNSCC and the possibility of their clinical translation in the context of engineered T cells and cancer vaccines is already being investigated in clinical trials
Summary
Head and neck squamous cell carcinoma (HNSCC), comprising cancers derived from the oral cavity, nasopharynx, oropharynx, hypopharynx, and larynx, accounted for 796,577 new cancer cases and 387,117 cancer-related deaths in 2020 worldwide [1,2]. There remains a pressing clinical need to improve the therapeutic arsenal against this disease. HPV-positive HNSCCs exhibit a distinct clinical course compared to HPV-negative disease. Patients with HPV-associated oropharyngeal cancers have improved prognosis compared to those with HPV-negative cancers due in part to enhanced responsiveness to chemotherapy and radiotherapy [4]. Given the motivation to alleviate treatment-associated morbidity and the recognition that a subset of HPV-positive HNSCC patients has a poor prognosis, there is a need to identify biomarkers that define patient subgroups by prognosis or likelihood of safe response to treatment de-escalation [4,8]. Why most HPV-positive HNSCCs have a better prognosis compared to HPVnegative is a question of interest in the field. Cancer/testis antigens represent a compelling class of molecules that may fill a niche in each of these research needs
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