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探索通读诱导分子 2, 6-二氨基嘌呤在增强针对癌细胞的免疫反应中的作用

英文原题:Exploring the role of readthrough-inducing molecule 2,6-diaminopurine to increase immune response against cancer cells.

查看英文原题

Exploring the role of readthrough-inducing molecule 2,6-diaminopurine to increase immune response against cancer cells.

PubMed 2025/09/12(内容时间) Mol Ther Q1 · IF 11.4(JCR 2025)

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中文摘要

免疫肿瘤治疗是一种极具前景的治疗策略,依赖于癌细胞在其表面呈递特定抗原表位的能力。由于癌细胞快速增殖,它们经常积累遗传变异,包括提前终止密码子。在本研究中,我们探讨了2,6-二氨基嘌呤(DAP)——一种强效的翻译通读诱导分子——激发抗肿瘤免疫反应的潜力。DAP处理后产生的通读蛋白可通过主要组织相容性复合体展示在细胞表面,从而可能增强免疫识别。这一点通过一个编码FIREFLY LUCIFERASE的构建体得到了证明,该构建体被一个UGA终止密码子中断,并在其C端融合了SL8抗原肽。此外,体内暴露于DAP可促进免疫效应细胞(包括T淋巴细胞、巨噬细胞和NK 细胞)向肿瘤微环境的募集。这些发现表明,DAP以及其他潜在的翻译通读诱导分子有望成为抗肿瘤治疗的新型候选药物。

展开英文摘要原文

Immuno-oncotherapy is a highly promising therapeutic strategy that relies on the ability of cancer cells to present specific antigenic epitopes at their surfaces. Because they proliferate rapidly, cancer cells frequently accumulate genetic variants, including premature termination codons. In this study, we investigated the potential of 2,6-diaminopurine (DAP), a potent translational-readthrough-inducing molecule, to elicit an antitumor immune response.

Readthrough-resulting proteins following DAP treatment can be displayed at the cell surface by the major histocompatibility complex, thus potentially enhancing immune recognition. This was demonstrated using a construct encoding FIREFLY LUCIFERASE interrupted by a UGA stop codon and fused at its C terminus with the SL8 antigenic peptide.

Furthermore, in vivo exposure to DAP promotes the recruitment of immune effector cells, including T lymphocytes, macrophages, and natural killer cells, to the tumor microenvironment.

These findings suggest that DAP and potentially other translational readthrough-inducing molecules hold promise as novel candidate drugs for antitumor therapy.

论文信息

作者
Sandoval Pacheco C、Leroy AM、Derhourhi M、Cardon T、Leroy C、Jouy N、Com E、Guevel B
第一作者单位
University Lille, CNRS, INSERM, UMR9020-U1277 - CANTHER - Cancer Heterogeneity Plasticity and Resistance to Therapies, 59000 Lille, France.France
通讯作者单位
University Lille, CNRS, INSERM, UMR9020-U1277 - CANTHER - Cancer Heterogeneity Plasticity and Resistance to Therapies, 59000 Lille, France. Electronic address: fabrice.lejeune@inserm.fr.France
期刊
Molecular therapy : the journal of the American Society of Gene Therapy2025 Dec 3
原文标识
PubMed 40946162 · DOI 10.1016/j.ymthe.2025.09.024