Pyroptosis Remodeling Tumor Microenvironment to Enhance Pancreatic Cancer Immunotherapy Driven by Membrane Anchoring Photosensitizer.

Abstract

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+ 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.

• Authors: Meng Wang, Min Wu, Xingang Liu, Shiyi Shao, Junmin Huang, Bin Liu, Tingbo Liang
• Journal: Advanced science (Weinheim, Baden-Wurttemberg, Germany) (Adv Sci (Weinh)) Vol. 9 Issue 29 Pg. e2202914 (Oct 2022) ISSN: 2198-3844 [Electronic] Germany
• PMID: 35981886 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.

Chemical References

• Immunologic Factors
• Photosensitizing Agents

Topics

• Humans
• Immunologic Factors (pharmacology)
• Immunotherapy (methods)
• Pancreatic Neoplasms (therapy)
• Photosensitizing Agents (pharmacology)
• Pyroptosis
• Tumor Microenvironment
• Pancreatic Neoplasms