在结直肠癌模型中,溶瘤呼肠孤病毒联合PD1-PDL1抑制剂增强CEA免疫治疗的效果。

IF 2.7 4区 医学 Q3 IMMUNOLOGY
Immunotherapy Pub Date : 2025-04-01 Epub Date: 2025-05-12 DOI:10.1080/1750743X.2025.2501926
Atefeh Yari, Seyed Younes Hosseini, Sanaz Asiyabi, Nazila Hajiahmadi, Mohammad Farahmand, Taravat Bamdad
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引用次数: 0

摘要

目的:溶瘤病毒联合免疫检查点抑制剂可提高肿瘤相关抗原疫苗免疫治疗的有效性。本研究在小鼠模型中评估溶瘤呼肠孤病毒与表达癌胚抗原(Ad-CEA)的腺载体和程序性死亡-1/程序性死亡配体1 (PD-1/PD-L1)抑制剂联合使用的疗效。方法:用Ad-CEA和PD-1/PD-L1抑制剂免疫携带表达cea的CT26肿瘤细胞的小鼠。随后,将三剂呼肠孤病毒注射到肿瘤中。检测肿瘤大小、组织病理学检查、CD8、FOXP3表达、脾T细胞淋巴细胞毒性、干扰素-γ (IFN-γ)、肿瘤坏死因子-α (TNF-α)分泌情况。结果:本研究中使用的三联疗法导致肿瘤生长最低,细胞毒性免疫水平最高。与其他对照组相比,肿瘤微环境中Foxp3水平和TNF-α分泌降低。此外,该组有丝分裂图数量最少,肿瘤浸润淋巴细胞数量最多。结论:肿瘤疫苗与溶瘤病毒联合使用可显著提高治疗效果。此外,在疫苗接种和病毒治疗期间抑制PD-1/PD-L1相互作用通过减少免疫抑制效应和刺激免疫系统来增强免疫病毒治疗,从而改善治疗结果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Oncolytic reovirus enhances the effect of CEA immunotherapy when combined with PD1-PDL1 inhibitor in a colorectal cancer model.

Aim: The effectiveness of immunotherapy with tumor associated antigen vaccines can be enhanced by combining oncolytic viruses with immune checkpoint inhibitors. This study evaluates the efficacy of oncolytic reovirus in combination with an adenovector expressing carcinoembryonic antigen (Ad-CEA) and a programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitor in a mouse model.

Methods: Mice bearing CEA-expressing CT26 tumor cells were immunized with Ad-CEA along with a PD-1/PD-L1 inhibitor. Subsequently, three doses of reovirus were injected into the tumors. Tumor size, histopathological examination, CD8 and FOXP3 expression, the cytotoxicity of spleen T cell lymphocytes, and the secretion of Interferon-γ (IFN-γ) and Tumor necrosis factor- α (TNF-α) were examined.

Results: The triple therapy used in this study resulted in the lowest tumor growth and the highest level of cytotoxic immunity. The Foxp3 levels in the tumor microenvironment and TNF-α secretion decreased compared to other control groups. Additionally, this group exhibited the lowest number of mitotic figures and the highest amount of tumor-infiltrating lymphocytes.

Conclusion: The combination of tumor vaccines with oncolytic viruses significantly improves treatment efficacy. Furthermore, inhibiting the PD-1/PD-L1 interaction during vaccination and also with virotherapy enhances immunovirotherapy by reducing immunosuppressive effects and stimulating the immune system, leading to improved therapeutic outcomes.

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来源期刊
Immunotherapy
Immunotherapy 医学-免疫学
CiteScore
5.00
自引率
3.60%
发文量
113
审稿时长
6-12 weeks
期刊介绍: Many aspects of the immune system and mechanisms of immunomodulatory therapies remain to be elucidated in order to exploit fully the emerging opportunities. Those involved in the research and clinical applications of immunotherapy are challenged by the huge and intricate volumes of knowledge arising from this fast-evolving field. The journal Immunotherapy offers the scientific community an interdisciplinary forum, providing them with information on the most recent advances of various aspects of immunotherapies, in a concise format to aid navigation of this complex field. Immunotherapy delivers essential information in concise, at-a-glance article formats. Key advances in the field are reported and analyzed by international experts, providing an authoritative but accessible forum for this vitally important area of research. Unsolicited article proposals are welcomed and authors are required to comply fully with the journal''s Disclosure & Conflict of Interest Policy as well as major publishing guidelines, including ICMJE and GPP3.
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