title: Thymosin α1 promotes the activation of myeloid-derived suppressor cells in a Lewis lung cancer model by upregulating Arginase 1.
abstract: Thymosin α1 (Tα1) has been tested for cancer therapy for several years, in most cases, the anti-tumor effect of Tα1 was limited, especially when Tα1 was used as a single agent. The role of Tα1 in cancer treatment and the regulatory mechanisms by which Ta1 takes effects are not yet completely understood. Using a Lewis lung caner model, here we report that Tα1 used alone elevated CD8(+) T cells, but failed to inhibit tumor growth. Furthermore, immunosuppressive myeloid-derived suppressor cells (MDSCs) showed heightened Arginase 1 production in response to Tα1 treatment, which led to stronger suppression of anti-tumor immunity. In addition, the upregulation of ARG1 was dependent on TLRs/MyD88 signaling, blocking MyD88 signaling abrogated the enhanced ARG1 expression and restored the anti-tumor efficacy of Tα1. This study provides the first demonstration that Tα1 treatment activates but not expands MDSCs via MyD88 signaling, which indicates better immunotherapeutic strategy of Tα1 against cancer.
authors.affiliation: Cancer Center, Chinese PLA General Hospital and Chinese PLA Medical School, 28 FuXing Road, Beijing 100853, PR China; International Joint Cancer Institute, The Second Military Medical University, 800 Xiang Yin Road, Shanghai 200433, PR China.
authors.forename: Chao
authors.initials: C
authors.lastname: Yuan
authors.affiliation: Department of Respiratory and Critical Care Medicine, Fuzong Clinical College of Fujian Medical University, Fuzhou General Hospital, Fuzhou, Fujian 350000, PR China.
authors.forename: Yisheng
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Cancer Center, Chinese PLA General Hospital and Chinese PLA Medical School, 28 FuXing Road, Beijing 100853, PR China; International Joint Cancer Institute, The Second Military Medical University, 800 Xiang Yin Road, Shanghai 200433, PR China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Cancer Center, Chinese PLA General Hospital and Chinese PLA Medical School, 28 FuXing Road, Beijing 100853, PR China.
authors.forename: LiJuan
authors.initials: L
authors.lastname: Shao
authors.affiliation: Cancer Center, Chinese PLA General Hospital and Chinese PLA Medical School, 28 FuXing Road, Beijing 100853, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Cancer Center, Chinese PLA General Hospital and Chinese PLA Medical School, 28 FuXing Road, Beijing 100853, PR China.
authors.forename: Tian
authors.initials: T
authors.lastname: Tian
authors.affiliation: Cancer Center, Chinese PLA General Hospital and Chinese PLA Medical School, 28 FuXing Road, Beijing 100853, PR China.
authors.forename: XiaoBin
authors.initials: X
authors.lastname: Gu
authors.affiliation: Department of Thoracic Surgery, First Affiliated Hospital of Zhengzhou University, No. 1, Jianshe Road, Zhengzhou 450052, PR China. Electronic address: lxn-2000@163.com.
authors.forename: Xiangnan
authors.initials: X
authors.lastname: Li
authors.affiliation: Cancer Center, Chinese PLA General Hospital and Chinese PLA Medical School, 28 FuXing Road, Beijing 100853, PR China; International Joint Cancer Institute, The Second Military Medical University, 800 Xiang Yin Road, Shanghai 200433, PR China. Electronic address: kexingfan@126.com.
authors.forename: KeXing
authors.initials: K
authors.lastname: Fan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001119:Arginase / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000401:mortality; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D007113:Immunity, Innate / Q000187:drug effects; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D016019:Survival Analysis; D000077596:Thymalfasin; D013947:Thymosin / Q000031:analogs & derivatives* / Q000494:pharmacology; D051193:Toll-Like Receptors / Q000235:genetics / Q000276:immunology
chemical_list: D000970:Antineoplastic Agents; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D051193:Toll-Like Receptors; D013947:Thymosin; C544448:Arg1 protein, mouse; D001119:Arginase; D000077596:Thymalfasin
keywords: Arginase 1; Lung cancer; MyD88; Myeloid-derived suppressor cells; Thymosin α1