REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1610858
This article is part of the Research TopicBreakthroughs in Immune Checkpoint Therapy: Overcoming Resistance with Novel TechniquesView all 6 articles
Synergy of Oncolytic Adenovirus and Immune Checkpoint Inhibitors: Transforming Cancer Immunotherapy Paradigms
Provisionally accepted
- Department of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
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Oncolytic viruses (OVs) offer a promising antitumor strategy by selectively lysing tumor cells and simultaneously activating innate and adaptive immune responses. Recent studies have shed light on the immunostimulatory mechanisms of OVs, particularly oncolytic adenovirus (OAds), which are emerging as leading candidates due to their favorable safety profile, genomic stability, and efficient transduction capacity. Despite the significant progress made by immune checkpoint inhibitors (ICIs) in antitumor therapy, treatment resistance continues to be a major barrier to their clinical effectiveness. OVs and ICIs work synergistically: OVs reprogram the immunosuppressive tumor microenvironment (TME) through immune cell recruitment and pro-inflammatory cytokine production, potentially overcoming ICI resistance. In turn, ICIs enhance T cell function by blocking inhibitory signaling pathways. This review highlights recent preclinical and clinical advancements in the therapeutic potential of combining OAds with ICIs, while also addressing critical translational challenges. We propose a strategic framework for optimizing the development and clinical trial design of these combination therapies to advance precision immunotherapy.
Keywords: oncolytic adenovirus, immune checkpoint inhibitors, Drug Resistance, Tumor Microenvironment, Immunotherapy
Received: 13 Apr 2025; Accepted: 23 Jun 2025.
Copyright: © 2025 Cheng, Wang and Zhang. 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: Shuang Zhang, Department of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
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