Experimental Oncology - Innovative Immunological Models, Istituto Nazionale per lo Studio e la Cura dei Tumori, "Fondazione Pascale"- IRCCS, Naples, Italy.
Esperimental Oncology - Molecular Biology and Viral Oncogenesis, Istituto Nazionale per lo Studio e la Cura dei Tumori, "Fondazione Pascale"- IRCCS, Naples, Italy.
J Immunother Cancer. 2021 May;9(5). doi: 10.1136/jitc-2021-002694.
The host's immune system develops in equilibrium with both cellular self-antigens and non-self-antigens derived from microorganisms which enter the body during lifetime. In addition, during the years, a tumor may arise presenting to the immune system an additional pool of non-self-antigens, namely tumor antigens (tumor-associated antigens, TAAs; tumor-specific antigens, TSAs).
In the present study, we looked for homology between published TAAs and non-self-viral-derived epitopes. Bioinformatics analyses and ex vivo immunological validations have been performed.
Surprisingly, several of such homologies have been found. Moreover, structural similarities between paired TAAs and viral peptides as well as comparable patterns of contact with HLA and T cell receptor (TCR) α and β chains have been observed. Therefore, the two classes of non-self-antigens (viral antigens and tumor antigens) may converge, eliciting cross-reacting CD8 T cell responses which possibly drive the fate of cancer development and progression.
An established antiviral T cell memory may turn out to be an anticancer T cell memory, able to control the growth of a cancer developed during the lifetime if the expressed TAA is similar to the viral epitope. This may ultimately represent a relevant selective advantage for patients with cancer and may lead to a novel preventive anticancer vaccine strategy.
宿主的免疫系统与细胞自身抗原以及在其一生中进入体内的微生物衍生的非自身抗原处于平衡状态。此外，随着时间的推移，肿瘤可能会出现，为免疫系统提供另一批非自身抗原，即肿瘤抗原（肿瘤相关抗原，TAA；肿瘤特异性抗原，TSA）。
在本研究中，我们寻找了已发表的 TAA 与非自身病毒衍生表位之间的同源性。进行了生物信息学分析和体外免疫验证。
令人惊讶的是，发现了其中的一些同源性。此外，还观察到配对的 TAA 与病毒肽之间存在结构相似性，以及与 HLA 和 T 细胞受体（TCR）α和β链的接触模式相似。因此，这两类非自身抗原（病毒抗原和肿瘤抗原）可能会趋同，引发交叉反应的 CD8 T 细胞反应，可能会影响癌症发展和进展的命运。
已建立的抗病毒 T 细胞记忆可能会转化为抗癌 T 细胞记忆，如果表达的 TAA 与病毒表位相似，则能够控制一生中发生的癌症的生长。这可能最终为癌症患者带来重要的选择性优势，并可能导致新的预防性抗癌疫苗策略。
