Multifunctional Nanoregulator Reshapes Immune Microenvironment and Enhances Immune Memory for Tumor Immunotherapy.

ABSTRACT: Hypoxia leads to up-regulation of PD-L1 and decreases T lymphocyte infiltration, thus boosting immunotherapeutic resistance of tumors. Moreover, tumor-infiltrating myeloid cells such as myeloid-derived suppressor cells (MDSCs) correlate with potent immune suppressive activity and resistance to the immune checkpoint blocking (ICB) in tumor sites. Here, a multifunctional nanoregulator incorporating MnO₂ particles and small molecular IPI549 is developed, which can reshape the tumor immune microenvironment (TIME) to unleash the immune system. The intravenously administered nanoregulator effectively accumulates in tumor sites to alleviate hypoxia via oxygen-generating reduction of MnO₂ and to inhibit PI3Kγ on MDSCs via IPI549 release in the tumor microenvironment (TME), wh

SUBMITTER: Yu M 

PROVIDER: S-EPMC6702652 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature