Stimuli-responsive nano vehicle enhances cancer immunotherapy by coordinating mitochondria-targeted immunogenic cell death and PD-L1 blockade.

ABSTRACT: Induction of immunogenic cell death promotes antitumor immunity against cancer. However, majority of clinically-approved drugs are unable to elicit sufficient ICD. Here, our study revealed that mitochondria-targeted delivery of doxorubicin (DOX) massively amplified ICD via substantial generation of reactive oxygen species (ROS) after mitochondrial damage. The underlying mechanism behind increased ICD was further demonstrated to be ascribed to two pathways: (1) ROS elevated endoplasmic reticulum (ER) stress, leading to surface exposure of calreticulin; (2) ROS promoted release of various mitochondria-associated damage molecules including mitochondrial transcription factor A. Nevertheless, adaptive upregulation of PD-L1 was found after such ICD-inducing treatment. To overcome such imm

SUBMITTER: Li Q 

PROVIDER: S-EPMC9136536 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature