Journal
ADVANCED SCIENCE
Volume 9, Issue 29, Pages -Publisher
WILEY
DOI: 10.1002/advs.202202914
Keywords
pyroptosis; photodynamic therapy; aggregation-induced emission; immunotherapy; pancreatic cancer
Categories
Funding
- National Natural Science Foundation for Young Scientists of China [21807092]
- National Key Research and Development Program of China [2019YFC1316000]
- National Natural Science Foundation of China [81830089]
- Singapore National Research Foundation [R279-000-483-281]
- National University of Singapore [R279-000-482-133]
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This study utilizes pyroptosis-induced immune responses to promote immunotherapy in pancreatic cancer, transforming the tumor microenvironment and inhibiting tumor growth while attacking distant tumors.
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.
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