4.8 Article

Relaxin gene delivery modulates macrophages to resolve cancer fibrosis and synergizes with immune checkpoint blockade therapy

期刊

SCIENCE ADVANCES
卷 7, 期 8, 页码 -

出版社

AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abb6596

关键词

-

资金

  1. NIH [CA198999]
  2. NSFC [51773176, 21975218]
  3. China Scholarship Council

向作者/读者索取更多资源

The study demonstrates that targeting gene delivery-induced RLN can modulate macrophages to reduce tumor-associated fibrosis and promote infiltration of anti-tumor T cells. In addition, RLN gene delivery synergizes with PD-L1 blockade to enhance the effectiveness of immunotherapy against tumors.
Cancer fibrosis serves as a major therapeutic barrier in desmoplastic tumors. Relaxin (RLN; a systemic hormone) is efficacious to decrease fibrosis, but the in vivo mechanism of action is not clear. Considering the localization of relaxin family peptide receptor type 1 (RXFP1), the receptor for RLN, on macrophages, we hypothesize that macrophages can be modulated by RLN to ameliorate cancer fibrosis. Using KPC mouse model of pancreatic ductal adenocarcinoma (PDAC), here, we report locally expressed RLN with targeted gene delivery induces increased F4/80(+)CD206(+) macrophages originating from Ly6C(+) monocytes, promoting fibrosis depletion and cytotoxic T cell infiltration. Moreover, RLN gene delivery synergizes with PD-L1 blockade for tumor inhibition by enhancing T cell-mediated tumor cell killing and macrophage phagocytosis. Collectively, our results reveal previously unidentified insights into the modulation of macrophages to regulate tumor-associated fibrosis, providing a feasible strategy to reverse the immunosuppressive environment and improve the therapeutic outcome of checkpoint immunotherapies.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.8
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据