Cavalluzzo Beatrice, Mauriello Angela, Ragone Concetta, Manolio Carmen, Tornesello Maria Lina, Buonaguro Franco M, Tvingsholm Siri Amanda, Hadrup Sine Reker, Tagliamonte Maria, Buonaguro Luigi
Innovative Immunological Models Unit, Istituto Nazionale Tumori-IRCCS-"Fond G. Pascale", 80131 Naples, Italy.
Molecular Biology and Viral Oncogenesis Unit, Istituto Nazionale Tumori-IRCCS-"Fond G. Pascale", 80131 Naples, Italy.
Cancers (Basel). 2021 Dec 28;14(1):140. doi: 10.3390/cancers14010140.
Hepatocellular carcinoma (HCC) is the third leading cause of death from cancer globally. Indeed, only a few treatments are available, most of which are effective only for the early stages of the disease. Therefore, there is an urgent needing for potential markers for a specifically targeted therapy. Candidate proteins were selected from datasets of The Human Protein Atlas, in order to identify specific tumor-associated proteins overexpressed in HCC samples associated with poor prognosis. Potential epitopes were predicted from such proteins, and homology with peptides derived from viral proteins was assessed. A multiparametric validation was performed, including recognition by PBMCs from HCC-patients and healthy donors, showing a T-cell cross-reactivity with paired epitopes. These results provide novel HCC-specific tumor-associated antigens (TAAs) for immunotherapeutic anti-HCC strategies potentially able to expand pre-existing virus-specific CD8 T cells with superior anticancer efficacy.
肝细胞癌(HCC)是全球癌症死亡的第三大主要原因。事实上,目前可用的治疗方法很少,其中大多数仅对疾病的早期阶段有效。因此,迫切需要用于特异性靶向治疗的潜在标志物。从人类蛋白质图谱的数据集中选择候选蛋白质,以鉴定在与不良预后相关的HCC样本中过表达的特定肿瘤相关蛋白质。从这些蛋白质中预测潜在的表位,并评估与病毒蛋白衍生肽的同源性。进行了多参数验证,包括来自HCC患者和健康供体的PBMC的识别,显示T细胞与配对表位的交叉反应性。这些结果为免疫治疗性抗HCC策略提供了新的HCC特异性肿瘤相关抗原(TAA),这些策略可能能够扩增预先存在的具有卓越抗癌功效的病毒特异性CD8 T细胞。