基于腺病毒的癌症免疫疗法中乙酰化的多层控制。

The multilayered control of acetylation during adenovirus-based immunotherapy of cancer.

作者信息

Parthasarathy Akhila, Frost Maria, Gillard Andrew G, Alonso Marta M, Gomez-Manzano Candelaria, Fueyo Juan

机构信息

Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

出版信息

Mol Ther Oncol. 2025 Mar 22;33(2):200976. doi: 10.1016/j.omton.2025.200976. eCollection 2025 Jun 18.

DOI:10.1016/j.omton.2025.200976

PMID:40236995

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11999684/

Abstract

Adenoviruses are highly immunogenic agents that have shown promise first as gene delivery vectors and later as oncolytic viruses. Currently, oncolytic adenoviruses are featured in over 30% of cancer virotherapy clinical trials. Due to their effective cellular uptake and hijack of cellular machinery, replication-competent adenoviruses are promising therapeutic agents for treating a wide range of tumors. Adenoviral influence on host cell acetylome regulation has regained attention, as these viruses redirect or suppress acetylation during replication, making them potentially desirable therapeutic agents for cancers driven by epigenetic modifications. In this review, we aim to cover the viral processes influencing the acetylome of the host genome. In addition, we shall discuss the effect of differential acetylation on the antiviral defense mounted by the host immune system. Lastly, we will discuss the opportunities for combining acetylation modifiers with oncolytic adenoviruses to improve further outcomes for patients treated with viroimmunotherapy.

摘要

腺病毒是高度免疫原性的病原体，最初作为基因递送载体显示出应用前景，后来又作为溶瘤病毒展现出潜力。目前，溶瘤腺病毒参与了超过30%的癌症病毒疗法临床试验。由于其有效的细胞摄取和对细胞机制的劫持，具有复制能力的腺病毒是治疗多种肿瘤的有前景的治疗剂。腺病毒对宿主细胞乙酰化组调控的影响重新受到关注，因为这些病毒在复制过程中改变或抑制乙酰化，使其成为由表观遗传修饰驱动的癌症潜在的理想治疗剂。在本综述中，我们旨在涵盖影响宿主基因组乙酰化组的病毒过程。此外，我们将讨论差异乙酰化对宿主免疫系统发起的抗病毒防御的影响。最后我们将探讨将乙酰化修饰剂与溶瘤腺病毒联合使用的机会，以进一步改善接受病毒免疫疗法治疗的患者的治疗效果。