One-dimensional nanosonosensitizer boosted multiple branches of immune responses against MHC-deficient immune-evasive urologic tumor.

Abstract

Cancer immunotherapies rely on CD8⁺ cytolytic T lymphocytes (CTLs) in recognition and eradication of tumor cells via antigens presented on major histocompatibility complex class I (MHC-I) molecules. However, we observe MHC-I deficiency in human and murine urologic tumors, posing daunting challenges for successful immunotherapy. We herein report an unprecedented nanosonosensitizer of one-dimensional bamboo-like multisegmented manganese dioxide@manganese-bismuth vanadate (BMMBV) to boost multiple branches of immune responses targeting MHC-I-deficient tumors. BMMBV markedly augments sonodynamic activity contributed by manganese heteroatoms in the lattice of bismuth vanadate with narrowing bandgaps. Under sonoirradiation, BMMBV enhances tumor antigen spreading and emission of adjuvant signals, which potentiate dendritic cell maturation, thereby eliciting high aptitude of CTLs. This therapy substantially up-regulates MHC expression on tumor cells, which are reversely sensitive to CTLs. Alongside, extensive innate immune cells complement the cytolytic activity of CTLs for eliminating mouse urologic tumors. This study offers a reinforced strategy against antigen-loss immune-evasive tumor.