期刊
ADVANCED SCIENCE
卷 9, 期 11, 页码 -出版社
WILEY
DOI: 10.1002/advs.202104619
关键词
checkpoint blockade; immunotherapy; myeloid cells; nanomedicine; tumor therapy
资金
- National Natural Science Foundation of China [81725008, 82171943, 81900491, 81801802, 81927801]
- Science and Technology Commission of Shanghai Municipality [19DZ2251100]
- Shanghai Municipal Health Commission [2019LJ21, SHSLCZDZK 03502]
- Shanghai Rising-Star Program [21QA1407200]
- Shanghai Pujiang Program [2019PJD039]
- Special Project for Clinical Research of Health Industry of Shanghai Health Commission [20214Y0151]
Inadequate ablation can result in an immunosuppressive microenvironment dominated by myeloid cells, leading to resistance to immune checkpoint blocking therapy. This study developed a scaffold system that delivers IPI549 and aPDL1 to disrupt the immunosuppressive microenvironment and enhance anti-tumor immune response. Preclinical models demonstrated that this biomaterial system mimics a hot tumor-immunity niche, inhibiting tumor progression and metastasis, and protecting cured mice against tumor rechallenge.
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.
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