Engineering ROS-Responsive Bioscaffolds for Disrupting Myeloid Cell-Driven Immunosuppressive Niche to Enhance PD-L1 Blockade-Based Postablative Immunotherapy.
Shaoyue LiChunyan ZhuXianli ZhouLiang ChenXiaowan BoYuting ShenXin GuanXiaoxia HanDandan ShanLiping SunYu ChenHuixiong XuWenwen YuePublished in: Advanced science (Weinheim, Baden-Wurttemberg, Germany) (2022)
The existence of inadequate ablation remains an important cause of treatment failure for loco-regional ablation therapies. Here, using a preclinical model, it is reported that inadequate microwave ablation (iMWA) induces immunosuppressive niche predominated by myeloid cells. The gene signature of ablated tumor presented by transcriptome analyses is highly correlated with immune checkpoint blocking (ICB) resistance. Thus, an in situ scaffold with synergistic delivery of IPI549 and anti-programmed death-ligand 1 blocking antibody (aPDL1) for postablative cancer immunotherapy is designed and engineered, in which IPI549 capable of targeting myeloid cells could disrupt the immunosuppressive niche and subsequently improve ICB-mediated antitumor immune response. Based on five mouse cancer models, it is demonstrated that this biomaterial system (aPDL1&IPI549@Gel) could mimic a "hot" tumor-immunity niche to inhibit tumor progression and metastasis, and protect cured mice against tumor rechallenge. This work enables a new standard-of-care paradigm for the immunotherapy of myeloid cells-mediated "cold" tumors after loco-regional inadequate practices.
Keyphrases
- induced apoptosis
- cell cycle arrest
- dendritic cells
- immune response
- bone marrow
- acute myeloid leukemia
- healthcare
- radiofrequency ablation
- primary care
- cell death
- single cell
- palliative care
- gene expression
- endoplasmic reticulum stress
- genome wide
- oxidative stress
- squamous cell carcinoma
- cell proliferation
- poor prognosis
- atrial fibrillation
- mesenchymal stem cells
- toll like receptor
- young adults
- adipose tissue
- skeletal muscle
- catheter ablation
- lymph node metastasis
- replacement therapy
- wound healing
- smoking cessation