title: Enhanced Anti-Tumor Efficacy through a Combination of Integrin αvβ6-Targeted Photodynamic Therapy and Immune Checkpoint Inhibition.
abstract: "Training" the host immune system to recognize and systemically eliminate residual tumor lesions and micrometastases is a promising strategy for cancer therapy. In this study, we investigated whether integrin αvβ6-targeted photodynamic therapy (PDT) of tumors using a phthalocyanine dye-labeled probe (termed DSAB-HK) could trigger the host immune response, and whether PDT in combination with anti-PD-1 immune checkpoint inhibition could be used for the effective therapy of primary tumors and metastases. By near-infrared fluorescence imaging, DSAB-HK was demonstrated to specifically target either subcutaneous tumors in a 4T1 mouse breast cancer model or firefly luciferase stably transfected 4T1 (4T1-fLuc) lung metastatic tumors. Upon light irradiation, PDT by DSAB-HK significantly inhibited the growth of subcutaneous 4T1 tumors, and in addition promoted the maturation of dendritic cells and their production of cytokines, which subsequently stimulated the tumor recruitment of CD8(+) cytotoxic T lymphocytes. Furthermore, DSAB-HK PDT of the first tumor followed by PD-1 blockade markedly suppressed the growth of a second subcutaneous tumor, and also slowed the growth of 4T1-fLuc lung metastasis as demonstrated by serial bioluminescence imaging. Together, our results demonstrated the synergistic effect of tumor-targeted PDT and immune checkpoint inhibition for improving anti-tumor immunity and suppressing tumor growth/metastasis.
authors.affiliation: 1. Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China;
authors.forename: Liquan
authors.initials: L
authors.lastname: Gao
authors.affiliation: 1. Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China;
authors.forename: Chenran
authors.initials: C
authors.lastname: Zhang
authors.affiliation: 1. Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China;
authors.forename: Duo
authors.initials: D
authors.lastname: Gao
authors.affiliation: 1. Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China;
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.affiliation: 1. Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China;
authors.forename: Xinhe
authors.initials: X
authors.lastname: Yu
authors.affiliation: 1. Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China;
authors.forename: Jianhao
authors.initials: J
authors.lastname: Lai
authors.affiliation: 1. Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China;
authors.forename: Fan
authors.initials: F
authors.lastname: Wang
authors.affiliation: 2. Synthetic and Functional Biomolecules Center, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Lin
authors.affiliation: 1. Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China;
authors.forename: Zhaofei
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism*; D001943:Breast Neoplasms / Q000628:therapy*; D018414:CD8-Positive T-Lymphocytes; D003602:Cytotoxicity, Immunologic; D004195:Disease Models, Animal; D007155:Immunologic Factors / Q000008:administration & dosage*; D007211:Indoles / Q000008:administration & dosage*; D016023:Integrins / Q000378:metabolism*; D054833:Isoindoles; D008027:Light; D008175:Lung Neoplasms / Q000556:secondary / Q000628:therapy*; D051379:Mice; D010778:Photochemotherapy / Q000379:methods*; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000951:Antigens, Neoplasm; D007155:Immunologic Factors; D007211:Indoles; D016023:Integrins; D054833:Isoindoles; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor; D011838:Radiation-Sensitizing Agents; C073878:integrin alphavbeta6; C013647:phthalocyanine
keywords: Checkpoint inhibition; Combination therapy.; Molecular imaging; Photodynamic therapy; Tumor metastasis