TLR7/8-agonist-loaded nanoparticles promote the polarization of tumour-associated macrophages to enhance cancer immunotherapy.

ABSTRACT: Tumour-associated macrophages are abundant in many cancers, and often display an immune-suppressive M2-like phenotype that fosters tumour growth and promotes resistance to therapy. Yet, macrophages are highly plastic and can also acquire an anti-tumorigenic M1-like phenotype. Here, we show that R848, an agonist of the toll-like receptors TLR7 and TLR8 identified in a morphometric-based screen, is a potent driver of the M1 phenotype in vitro and that R848-loaded β-cyclodextrin nanoparticles (CDNP-R848) lead to efficient drug delivery to tumour-associated macrophages in vivo. As a monotherapy, the administration of CDNP-R848 in multiple tumour models in mice altered the functional orientation of the tumour immune microenvironment towards an M1 phenotype, leading to controlled tumour growth a

SUBMITTER: Rodell CB 

PROVIDER: S-EPMC6192054 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature