Photodynamic-therapy Activates Immune Response by disrupting Immunity Homeostasis of Tumor Cells, which Generates Vaccine for Cancer Therapy

光动力疗法通过破坏肿瘤细胞的免疫稳态来激活免疫反应,从而产生癌症治疗疫苗。

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作者:Yuanhong Zheng ,Guifang Yin ,Vanminh Le ,Anle Zhang ,Siyu Chen ,Xin Liang ,Jianwen Liu

Abstract

Photodynamic therapy (PDT), a regulatory approved cancer treatment, is reported to be capable of causing immunogenic apoptosis. The current data reveal PDT can cause the dysregulation of "eat me" and "don't eat me" signal by generating reactive oxygen species (ROS) -mediated endoplasmic reticulum (ER) stress. This dysregulation probably contribute to the increased uptake of PDT-killed Lewis lung carcinoma (LLC) cells by homologous dendritic cells (DCs), accompanied by phenotypic maturation (CD80(high), CD86(high), and CD40(high)) and functional stimulation (NO(high), IL-10(absent)) of dendritic cells as well as subsequent T-cell responses. Morevover, C57BL/6 mice vaccinated with dendritic cells (DCs) pulsed with PDT-treated LLCs (PDT-DCs) or PDT-treated LLCs alone (PDT-LLCs) exhibited potent immunity against LLC tumors. In the current study, the PDT-induced immune response was characterized as a process related with the dysregulation of "eat me" signal and "don't eat me" signal, revealing the possibility for developing PDT into an antitumor vaccination strategy for personalized cancer immunotherapy. Keywords: Antitumor vaccination; CD47; DAMPs; Hypericin; Immunogenic apoptosis.

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