title: Photodynamic therapy-mediated cancer vaccination enhances stem-like phenotype and immune escape, which can be blocked by thrombospondin-1 signaling through CD47 receptor protein.
abstract: Like most of the strategies for cancer immunotherapy, photodynamic therapy-mediated vaccination has shown poor clinical outcomes in application. The aim of this study is to offer a glimpse at the mechanisms that are responsible for the failure based on cancer immuno-editing theory and to search for a positive solution. In this study we found that tumor cells were able to adapt themselves to the immune pressure exerted by vaccination. The survived tumor cells exhibited enhanced tumorigenic and stem-like phenotypes as well as undermined immunogenicity. Viewed as a whole, immune-selected tumor cells showed more malignant characteristics and the ability of immune escape, which might contribute to the eventual relapse. Thrombospondin-1 signaling via CD47 helped prevent tumor cells from becoming stem-like and rendered them vulnerable to immune attack. These findings prove that the TSP-1/CD47/SIRP-α signal axis is important to the evolution of tumor cells in the microenvironment of immunotherapy and identify thrombospondin-1 as a key signal with therapeutic benefits in overcoming long term relapse, providing new evidence for the clinical promise of cancer vaccination.
authors.affiliation: From the Department of Molecular and Cellular Pharmacology, Biomedical Nanotechnology Center, State Key Laboratory of Bioreactor Engineering and Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China and.
authors.forename: Yuanhong
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: From the Department of Molecular and Cellular Pharmacology, Biomedical Nanotechnology Center, State Key Laboratory of Bioreactor Engineering and Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China and.
authors.forename: Fangyuan
authors.initials: F
authors.lastname: Zou
authors.affiliation: From the Department of Molecular and Cellular Pharmacology, Biomedical Nanotechnology Center, State Key Laboratory of Bioreactor Engineering and Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China and.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Wang
authors.affiliation: From the Department of Molecular and Cellular Pharmacology, Biomedical Nanotechnology Center, State Key Laboratory of Bioreactor Engineering and Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China and.
authors.forename: Guifang
authors.initials: G
authors.lastname: Yin
authors.affiliation: From the Department of Molecular and Cellular Pharmacology, Biomedical Nanotechnology Center, State Key Laboratory of Bioreactor Engineering and Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China and.
authors.forename: Vanminh
authors.initials: V
authors.lastname: Le
authors.affiliation: Department of General Surgery, Xinhua Hospital Chongming Branch, Shanghai Jiaotong University School of Medicine, 25 Nanmen Road, Chengqiaozhen, Chongming Shanghai, 202150, China zheweifei@xinhuamed.com.cn.
authors.forename: Zhewei
authors.initials: Z
authors.lastname: Fei
authors.affiliation: From the Department of Molecular and Cellular Pharmacology, Biomedical Nanotechnology Center, State Key Laboratory of Bioreactor Engineering and Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China and liujian@ecust.edu.cn.
authors.forename: Jianwen
authors.initials: J
authors.lastname: Liu
mesh_terms: D000818:Animals; D051928:CD47 Antigen / Q000276:immunology / Q000378:metabolism*; D019496:Cancer Vaccines / Q000008:administration & dosage*; D016130:Immunophenotyping; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000276:immunology*; D010778:Photochemotherapy; D015398:Signal Transduction; D019700:Thrombospondin 1 / Q000378:metabolism*; D019139:Tumor Escape
chemical_list: D051928:CD47 Antigen; D019496:Cancer Vaccines; C497895:Cd47 protein, mouse; D019700:Thrombospondin 1; C585483:Thbs1 protein, mouse
keywords: CD47; Cancer Stem Cells; Immunotherapy; Photodynamic Therapy; Tumor Immunology; Tumor Microenvironment