2. Academic Validation
  3. Pyroptosis Remodeling Tumor Microenvironment to Enhance Pancreatic Cancer Immunotherapy Driven by Membrane Anchoring Photosensitizer

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

  • Adv Sci (Weinh). 2022 Aug 18;e2202914. doi: 10.1002/advs.202202914.
Meng Wang 1 2 3 4 5 6,  Min Wu 7 8,  Xingang Liu 7,  Shiyi Shao 1 2 3 4 5 6,  Junmin Huang 1 2 3 4 5 6,  Bin Liu 7 8,  Tingbo Liang 1 2 3 4 5 6
Affiliations

Affiliations

  • 1 Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University, School of Medicine, Hangzhou, 310003, P. R. China.
  • 2 Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, 310003, P. R. China.
  • 3 Innovation Center for the Study of Pancreatic Diseases, Hangzhou, 310003, P. R. China.
  • 4 Zhejiang Provincial Clinical Research Center for the Study of Hepatobiliary & Pancreatic Diseases, Hangzhou, 310003, P. R. China.
  • 5 Cancer Center, Zhejiang University, Hangzhou, 310058, P. R. China.
  • 6 Research Center for Healthcare Data Science, Zhejiang Lab, Hangzhou, 310003, P. R. China.
  • 7 Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore, 117585, Singapore.
  • 8 Joint School of National University of Singapore and Tianjin University, International Campus of Tianjin University, Binhai New City, Fuzhou, 350207, P. R. China.
PMID: 35981886 DOI: 10.1002/advs.202202914
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.

Keywords

aggregation-induced emission; immunotherapy; pancreatic cancer; photodynamic therapy; pyroptosis.

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