Innovative Immunological Models Unit, Istituto Nazionale Tumori - IRCCS - "Fond G. Pascale", Via Mariano Semmola, 52, Naples, Italy.
Molecular Biology and Viral Oncogenesis Unit, Istituto Nazionale Tumori - IRCCS - "Fond G. Pascale", Naples, Italy.
J Transl Med. 2022 Oct 15;20(1):472. doi: 10.1186/s12967-022-03681-4.
People living with HIV/AIDS (PLWHA) show a reduced incidence for three cancer types, namely breast, prostate and colon cancers. In the present study, we assessed whether a molecular mimicry between HIV epitopes and tumor associated antigens and, consequently, a T cell cross-reactivity could provide an explanation for such an epidemiological evidence.
Homology between published TAAs and non-self HIV-derived epitopes have been assessed by BLAST homology. Structural analyses have been performed by bioinformatics tools. Immunological validation of CD8 T cell cross-reactivity has been evaluated ex vivo by tetramer staining.
Sequence homologies between multiple TAAs and HIV epitopes have been found. High structural similarities between the paired TAAs and HIV epitopes as well as comparable patterns of contact with HLA and TCR α and β chains have been observed. Furthermore, cross-reacting CD8 T cells have been identified.
This is the first study showing a molecular mimicry between HIV antigens an TAAs identified in breast, prostate and colon cancers. Therefore, it is highly reasonable that memory CD8 T cells elicited during the HIV infection may play a key role in controlling development and progression of such cancers in the PLWHA lifetime. This represents the first demonstration ever that a viral infection may induce a natural "preventive" anti-cancer memory T cells, with highly relevant implications beyond the HIV infection.
HIV/AIDS（艾滋病毒/艾滋病）感染者（PLWHA）患三种癌症（乳腺癌、前列腺癌和结肠癌）的发病率降低。本研究评估了 HIV 表位与肿瘤相关抗原之间是否存在分子模拟，以及由此产生的 T 细胞交叉反应是否可以解释这种流行病学证据。
通过 BLAST 同源性评估已发表的 TAA 与非自身 HIV 衍生表位之间的同源性。通过生物信息学工具进行结构分析。通过四聚体染色，在体外评估 CD8 T 细胞交叉反应的免疫验证。
在多个 TAA 和 HIV 表位之间发现了序列同源性。配对的 TAA 和 HIV 表位之间存在高度的结构相似性，并且与 HLA 和 TCR α 和 β 链的接触模式也相似。此外，还鉴定出了交叉反应的 CD8 T 细胞。
这是第一项表明 HIV 抗原与乳腺癌、前列腺癌和结肠癌中鉴定的 TAA 之间存在分子模拟的研究。因此，在 HIV 感染期间产生的记忆 CD8 T 细胞很可能在 PLWHA 一生中控制这些癌症的发展和进展中发挥关键作用，这是首次证明病毒感染可能会诱导一种天然的“预防性”抗癌记忆 T 细胞，这对 HIV 感染以外的领域具有重要意义。
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