title: Systemic injection of TLR1/2 agonist improves adoptive antigen-specific T cell therapy in glioma-bearing mice.
abstract: Adoptive immunotherapy is an attractive strategy for glioma treatment. However, some obstacles still need be overcome. In this study, GL261-bearing mice treated with adoptively transferred antigen-specific T cells and systemic injection of bacterial lipoprotein (BLP), a TLR1/2 agonist, got a long-term survival and even immune protection. By analyzing adoptive T cells, it was found that BLP maintained T cell survival, proliferation and anti-tumor efficacy in the brains of tumor-bearing hosts. Moreover, tumor microenvironment was modified by up-regulating IFN-γ-secreting CD8+ T cells and down-regulating MDSC, which might be related with high CXCL10 and low CCL2 expression. In addition, TLR2 deficiency abrogated therapeutic effect with increased MDSC accumulation and decreased IFN-γ-secreting CD8+ T cells in the brains. Thus, the systemic injection of BLP could improve the adoptive T cell therapy by maintaining T cell persistence, modifying the tumor microenvironment and even inducing systemic anti-tumor immunity, which might offer a clinically promising immunotherapeutic strategy for glioma.
authors.affiliation: Department of Immunology, School of Basic Medical Sciences and Biotherapy Research Center, Fudan University, Shanghai, China.
authors.forename: Yufei
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Immunology, School of Basic Medical Sciences and Biotherapy Research Center, Fudan University, Shanghai, China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Luo
authors.affiliation: Department of Radiology, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Anning
authors.initials: A
authors.lastname: Li
authors.affiliation: Department of Immunology, School of Basic Medical Sciences and Biotherapy Research Center, Fudan University, Shanghai, China.
authors.forename: Jiawen
authors.initials: J
authors.lastname: Qian
authors.affiliation: Department of Radiology, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Zhenwei
authors.initials: Z
authors.lastname: Yao
authors.affiliation: Department of Radiology, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Feng
authors.affiliation: Department of Immunology, School of Basic Medical Sciences and Biotherapy Research Center, Fudan University, Shanghai, China. Electronic address: ywchu@shmu.edu.cn.
authors.forename: Yiwei
authors.initials: Y
authors.lastname: Chu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001932:Brain Neoplasms / Q000628:therapy*; D018414:CD8-Positive T-Lymphocytes / Q000637:transplantation*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D064987:Cell- and Tissue-Based Therapy; D005260:Female; D005434:Flow Cytometry; D005910:Glioma / Q000628:therapy*; D016219:Immunotherapy, Adoptive; D008074:Lipoproteins / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction; D051194:Toll-Like Receptor 1 / Q000819:agonists*; D051195:Toll-Like Receptor 2 / Q000819:agonists*
chemical_list: D000970:Antineoplastic Agents; D008074:Lipoproteins; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2
keywords: Adoptive T cell therapy;; Bacterial lipoprotein;; Glioma;; Toll-like receptor 2;; Tumor microenvironment