Nanoparticle induction of antigen-presenting monocyte-derived dendritic cells relieves immunosuppression and inhibits...

Myeloid immune cells play a major role in establishing a suitable microenvironment for metastasis by suppressing antigen-presentation pathways and effector T cell responses at metastatic sites, and reprogramming these cells may enhance anti-tumor cytotoxicity. Herein, we target myeloid cells with intravenously delivered nanoparticles to reduce the accumulation of neutrophils at the metastatic niche and induce the differentiation of monocytes into monocyte-derived dendritic cells (moDCs). Internalization of nanoparticles was linked to increased antigen presentation, T cell stimulation, and activation of Th1 cells. Nanoparticle administration increased the proportion of Th1 and Th17 CD4⁺ cells and did not inhibit metastasis in mice where monocytes or T cells were depleted, indicating that interactions between moDCs and T cells are essential to the mechanism of action. Our findings demonstrate that nanoparticles reprogram circulating monocytes into antigen-presenting moDCs, which are necessary to modulate the immunosuppressive microenvironment and upregulate anti-tumor helper T cell populations within the metastatic niche.