Skip to main content

REVIEW article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1535647
This article is part of the Research Topic Innovative Therapeutic Approaches for Complex Cancers: Exploring New Strategies in Glioblastoma, Urogenital, and Bladder Cancers View all articles

Extracellular matrix re-normalization to improve cold tumor penetration by oncolytic viruses

Provisionally accepted
Geofrey F. Soko Geofrey F. Soko 1Benson K. Kosgei Benson K. Kosgei 1Stephene S. Meena Stephene S. Meena 1Ying Jing Ng Ying Jing Ng 1Huihui Liang Huihui Liang 1Zhang Bing Zhang Bing 2Qingjun Liu Qingjun Liu 3Tielong Xu Tielong Xu 1Xinju Hou Xinju Hou 4Ray P.S. Han Ray P.S. Han 1*
  • 1 Jiangxi University of Chinese Medicine, Nanchang, China
  • 2 The Affiliated Hospital of Jiangxi University of Chinese Medicine, Nanchang, China
  • 3 Zhejiang University, Hangzhou, Zhejiang Province, China
  • 4 Nanchang Hongdu Hospital of Traditional Chinese Medicine, Nanchang, Jiangxi Province, China

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

    Immunologically inert or cold tumors pose a substantial challenge to the effectiveness of immunotherapy. The use of oncolytic viruses (OVs) to induce immunogenic cell death (ICD) in tumor cells is a well-established strategy for initiating the cancer immunity cycle (CIC). This process promotes the traf¬ficking and infiltration of CD8+ T cells into tumors, thereby eliciting a tumor-specific immune response. Despite the potential of OVs for handling cold tumors, clinical outcomes have fallen short of expec¬tations. To better understand the obstacles faced by onco¬lytic virus immunotherapy (OVI), we would like to revisit the OV issue. Growing evidence indicates that limited intratumoral pene¬tration and inadequate intratumoral distribution of OVs are critical factors contributing to the suboptimal response to OVI. Aberrant expres¬sions of matrix proteins by cancer-associated fibro-blasts (CAFs) alter the mechanical properties of the tumor extracellu¬lar matrix (ECM). This results in increased ECM desmoplasia and ele¬vated intra¬tumoral interstitial fluid pressure (IFP), creating physical barriers that impede the penetration and dissemination of OVs within tumors. This review explores the latest advancements in strategies designed to improve the intratumoral penetration of OVs to facilitate the penetration of tumor-infiltrating lympho¬cytes (TILs) into cold tumors. Additionally, we investigated current clinical trials and challenges associated with translating these strategies into clinical practice to improve patient outcomes.

    Keywords: cold tumors, Tumor immune microenvironment, Immunotherapy, Oncolytic Viruses, Tumor-infiltrating immune cells, Tumor ECM barriers

    Received: 27 Nov 2024; Accepted: 18 Dec 2024.

    Copyright: © 2024 Soko, Kosgei, Meena, Ng, Liang, Bing, Liu, Xu, Hou and Han. 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: Ray P.S. Han, Jiangxi University of Chinese Medicine, Nanchang, 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.