Immunotherapy, the most promising strategy of cancer treatment, has achieved promising outcomes, but its clinical efficacy in pancreatic cancer is limited mainly due to the complicated tumor immunosuppressive microenvironment. As a highly inflammatory form of immunogenic cell death (ICD), pyroptosis provides a great opportunity to alleviate immunosuppression and promote systemic immune responses in solid tumors. Herein, membrane-targeted photosensitizer TBD-3C with aggregation-induced emission (AIE) feature to trigger pyroptosis-aroused cancer immunotherapy via photodynamic therapy (PDT) is applied. The results reveal that pyroptotic cells induced by TBD-3C could stimulate M1-polarization of macrophages, cause maturation of dendritic cells (DCs), and activation of CD8<sup>+</sup> cytotoxic T-lymphocytes (CTLs). Pyroptosis-aroused immunological responses could convert immunosuppressive "cold" tumor microenvironment (TME) to immunogenic "hot" TME, which not only inhibits primary pancreatic cancer growth but also attacks the distant tumor. This work establishes a platform with high biocompatibility for light-controlled antitumor immunity and solid tumor immunotherapy aroused by cell pyroptosis.
Keyphrases
- photodynamic therapy
- nlrp inflammasome
- dendritic cells
- immune response
- cell death
- fluorescence imaging
- cell cycle arrest
- single cell
- stem cells
- induced apoptosis
- gene expression
- machine learning
- lymph node
- deep learning
- drug delivery
- regulatory t cells
- bone marrow
- adipose tissue
- dna methylation
- insulin resistance
- genome wide
- pi k akt
- endoplasmic reticulum stress
- mesenchymal stem cells
- weight loss
- neural network