Open AccessPyroptosis Remodeling Tumor Microenvironment to Enhance Pancreatic Cancer Immunotherapy Driven by Membrane Anchoring Photosensitizer
Author(s) -
Wang Meng,
Wu Min,
Liu Xingang,
Shao Shiyi,
Huang Junmin,
Liu Bin,
Liang Tingbo
Publication year - 2022
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.202202914
Subject(s) - tumor microenvironment , pyroptosis , immunotherapy , cancer research , pancreatic cancer , photodynamic therapy , cancer immunotherapy , immune system , cytotoxic t cell , cd8 , medicine , cancer , immunology , biology , chemistry , inflammation , inflammasome , in vitro , biochemistry , organic chemistry
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.