免疫系统
背向效应
癌症研究
肿瘤微环境
CD8型
FOXP3型
免疫疗法
T细胞
免疫检查点
免疫学
抗原
医学
作者
Kin Man Au,J. S. Swinnea,Andrew Z. Wang
标识
DOI:10.1002/adma.202411330
摘要
Abstract Radiotherapy (XRT) is often utilized to improve the immune checkpoint blockade response in cancer management. Such combination treatment can enhance the abscopal effect, facilitating a prolonged and durable systemic response. However, despite intense research efforts, only a minority of patients respond to this approach, and novel strategies to increase the abscopal effect are urgently needed. Here, the development of an intratumoral (i.t.) injectable nanofiber (NF)‐based tumor immune niche (TIN) that converts XRT‐treated tumors into an in situ cancer vaccine, eliciting robust systemic antitumor immunity, is reported. This NF‐based immune niche incorporates redox‐degradable anti‐CTLA‐4 (α‐CTLA‐4) nanogels (NGs) and interleukin‐2 (IL‐2) NGs for controlled release in hypoxic irradiated tumors, reversing the immunosuppressive tumor microenvironment into a pro‐inflammatory microenvironment, and expanding the tumor‐infiltrating CD8 + T cell population. Additionally, it is functionalized with polyinosinic‐polycytidylic acid (poly(I:C)) to promote antigen‐presenting cell maturation and prime neoantigen‐specific CD8 + T cells. In vitro studies demonstrate TIN's ability to prime antigen‐specific CD8 + T cells and increase antigen‐specific cell‐killing efficiency under in vitro immunosuppressive conditions. In vivo studies confirm TIN's ability to elicit robust systemic anticancer activity in mouse melanoma and colorectal cancer models without inducing severe immune‐related adverse events.
科研通智能强力驱动
Strongly Powered by AbleSci AI