Controlling T cell-tumor cell interaction with a biomimetic physical barrier for cancer immunotherapy

• 成果类型: Article
• 署名作者: Zhang, Yuxuan; Wang, Jinjin; Qing, Guangchao; Wang, Yongchao; Li, Xianlei; Luo, Ting; Wang, Yi - Feng; Liu, Lu; Wang, Yufei; Ni, Qiankun; Li, Shuyi; Chen, Junge; Li, Fangzhou; Guo, Weisheng; Zhang, Jinchao; Gong, Ningqiang; Liang, Xing - Jie
• 署名单位: Chinese Academy of Sciences; National Center for Nanoscience & Technology, CAS; Key Laboratory for Biological Effects of Nanomaterials & Nanosafety, CAS; Chinese Academy of Sciences; University of Chinese Academy of Sciences, CAS; Guangzhou Medical University; Guangzhou Medical University; Hebei University; Chinese Academy of Sciences; University of Science & Technology of China, CAS
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-9629
• DOI: 10.1073/pnas.2500589122
• 发表日期: 2025-07-15
• 关键词: peg-pcl; resistance; hydrogels; infiltration; pd-1

摘要

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.