Pegylated liposomal mitoxantrone modulates tumor immune landscape to boost PD-L1 blockade therapy

Abstract

Nanoparticles have great advantages in overcoming the delivery barriers for chemotherapeutics, but the effect on overall tumor immune landscape after drug delivery is still poorly understood. Here, we employed pegylated liposomal mitoxantrone (PL-MIT), an antitumor nanomedicine commercially approved by National Medical Products Administration, to systematically investigate its effects on tumor immune landscape. We found PL-MIT is able to significantly enhance multiple damage-associated molecule patterns (DAMPs) signals in tumors in vivo and evoke strong antitumor immunity by promoting the dendritic cells maturation and T cells infiltration. More importantly, we found that in addition to up-regulating the expression of PD-L1 on tumor cells, PL-MIT tends to induce high expression of PD-L1 on myeloid-derived suppressor cells (MDSC), especially on granulocytic MDSC (G-MDSC), which is unfavorable for the antitumor immunity. Under the guidance of these results, we combined the PL-MIT treatment with anti-PD-L1 antibody and found that the antitumor efficacy was further improved in anti-PD-L1 antibody-insensitive tumors. In summary, our study provides a new insight for the guiding of combination of nanomedicine and antitumor immunotherapy by investigating the impact of nanomedicine on the tumor immune landscape.