Skip to main content

ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1513555
This article is part of the Research Topic Vector-Based Gene Delivery in Cancer Immunotherapy View all 5 articles

Expression of SIRPα-Fc by Oncolytic Virus Enhances Antitumor Efficacy through Tumor Microenvironment Reprogramming

Provisionally accepted
Qingzhe Yang Qingzhe Yang 1Yongheng Shu Yongheng Shu 1Yanwei Chen Yanwei Chen 1Zhongbing Qi Zhongbing Qi 1Shichuan Hu Shichuan Hu 1Yao Zhang Yao Zhang 1Yu Qin Yu Qin 1Xianglin Xu Xianglin Xu 1Jianchuan Hu Jianchuan Hu 1Anliang Huang Anliang Huang 2Ping Cheng Ping Cheng 1*
  • 1 Sichuan University, Chengdu, China
  • 2 Chengdu Fifth People's Hospital, Chengdu, Sichuan Province, China

The final, formatted version of the article will be published soon.

    Oncolytic viruses (OVs) selectively replicate within tumors, directly killing cancer cells and promoting a systemic immune response by releasing tumor antigens. These features make OVs a promising approach in tumor immunotherapy, offering targeted treatment with fewer side effects. Despite these advantages, OVs are primarily administered via intratumoral injection, limiting their effectiveness for advanced, systemic cancers. Among OVs, oncolytic adenoviruses (oAdVs) are the most widely studied due to their well-understood gene regulation, safety, and stability. In this study, a modified oAdV vector, pDC316-oAd-SA, was engineered to express the SIRPα-mIgG1Fc gene, designed to remodel tumor-associated macrophages (TAMs) and enhance anti-tumor immunity. This vector, along with a control virus (Ad-ON), was evaluated both in vitro and in vivo. The modified oAd-SA significantly improved macrophage phagocytosis and showed superior tumor regression in murine models.Additionally, while both oAdVs increased T cell infiltration in the tumor microenvironment, oAd-SA specifically enhanced T cell immune function. The study also revealed that oAdVs modulate TAMs differently across tumor types, with oAd-SA therapy particularly increasing TAM phagocytosis and promoting an anti-tumor response.

    Keywords: Tumor-associated macrophages, Oncolytic adenovirus, SIRPα, Tumor immunotherapy, Tumor microenvironment Abbreviations ADCP, antibody-dependent cellular phagocytosis, DCs, dendritic cells, Foxp3, Forkhead box protein P3, ITIMs, immunoreceptor tyrosine-based inhibition motifs, MDSCs, myeloid-derived suppressor cells, MV, measles virus, OVs, oncolytic viruses, oAdVs, oncolytic adenoviruses

    Received: 18 Oct 2024; Accepted: 05 Feb 2025.

    Copyright: © 2025 Yang, Shu, Chen, Qi, Hu, Zhang, Qin, Xu, Hu, Huang and Cheng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Ping Cheng, Sichuan University, Chengdu, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.