2025-07-14 中国科学院(CAS)
- https://english.cas.cn/newsroom/research_news/life/202507/t20250715_1047367.shtml
- https://www.pnas.org/doi/10.1073/pnas.2500589122
がん免疫療法のためのバイオミメティック物理的バリアによるT細胞-腫瘍細胞相互作用の制御 Controlling T cell–tumor cell interaction with a biomimetic physical barrier for cancer immunotherapy
Yuxuan Zhang, Jinjin Wang, Guangchao Qing, +13 , and Xing-Jie Liang
Proceedings of the National Academy of Sciences Published:July 8, 2025
DOI:https://doi.org/10.1073/pnas.2500589122
Significance
Cancer immunotherapy often fails because infiltrating T cells in the tumor microenvironment are suppressed by immunosuppressive signals, leading to dysfunction and exhaustion. This study demonstrates a therapeutic strategy based on a physical barrier created by a hydrogel, which establishes a protective zone for T cells within the tumor microenvironment. This approach enables T cell accumulation and delays T cell exhaustion process, effectively suppressing tumor growth. When combined with OX40 antibody therapy, this strategy achieves a 50% tumor cure rate. These findings provide a perspective for cancer treatment, bridging materials science and immunology to address critical challenges in immunotherapy.
Abstract
Cancer immunotherapy has shown tremendous promise in various cancers. However, current strategies, such as immune checkpoint blockade, primarily restore exhausted T cells but provide only transient efficacy, as the rapid clearance of antibodies. Their limited durability is further hindered by persistent T cell-tumor cell interactions that accelerate T cell exhaustion. To prevent T cells from sustained exposure to these interactions, we present a hydrogel-based biomimetic physical barrier (BPB) here to create a “protective zone” for T cells. The BPB temporarily blocks T cell-tumor cell interactions and shields T cells from inactivation and exhaustion, allowing them to accumulate and maintain their functional activity in the tumor microenvironment. After sufficient T cell accumulation, the dismantling of BPB triggered by near-infrared light irradiation-induced gel-sol transition will restore the interaction between T cells and tumor cells. This controlled re-exposure allows the accumulated T cells to attack the tumor cells in a more activated and anti-exhaustion state, maximizing their tumor-killing potential. Moreover, BPB not only enhances immediate tumor regression but also triggers systemic immune activation and durable memory responses, enabling long-term protection against tumor rechallenge and effective control of multifocal tumors. Collectively, our BPB for modulating the T cell-tumor cell interaction has great prospects for advancing cancer immunotherapy.
