机构：[1]Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE and State Key Laboratory of Biotherapy, West China Second Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, P. R. China.[2]Division of Regenerative Medicine, Department of Medicine, University of California, San Diego, CA, U.S.A.[3]Department of Pathology, Case Western Reserve University, Cleveland, OH, U.S.A.[4]Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon, Republic of Korea[5]State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, P. R. China.[6]Department of Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, P.R. China.四川大学华西医院[7]College of Life Science, Sichuan University, Chengdu, P. R. China.[8]Department of Rheumatology and Immunology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu, P. R. China四川大学华西医院[9]Department of Biology and Biochemistry, Center for Nuclear Receptors and Cell Signaling, University of Houston, U.S.A[10]Department of Biosciences and Nutrition at NOVUM, Karolinska Institute, Sweden
The emerging immune checkpoint blockade (ICB) therapy has ushered the cancer therapeutics field into an era of immunotherapy. Although ICB treatment provides remarkable clinical responses in a subset of patients with cancer, this regimen fails to extend survival in a large proportion of patients. Here, we found that a combined treatment of estrogen receptor beta (ERβ) agonist and PD-1 antibody treatment improved therapeutic efficacy in mouse tumor models, compared with monotherapies, by reducing infiltration of myeloid-derived suppressor cells (MDSCs) and increasing CD8+ T cells in tumors. Mechanistically, LY500307 treatment reduced tumor-derived CSF1 and decreased infiltration of CSF1R+ MDSCs in the tumor bed. CSF1 released by tumor cells induced CSF1R+ MDSC chemotaxis in vitro and blockade of CSF1R demonstrated similar therapeutic effects as ERβ activation in vivo. Collectively, our study proved combined treatment of ERβ agonist and PD-1 antibody reduced MDSC infiltration in the tumor and enhanced tumor response to ICB therapy.
基金：
This work was supported by grants from National Natural Science Foundation of China(grant #81822034, grant # 81821002 and grant #81773119), National Key Research and Development Program of China(grant #2018YFA0109200 and grant#2017YFA0106800), Sichuan Science-Technology International Cooperation Project(grant #2019YFH0144), Direct Scientific Research Grants from West China Second Hospital, Sichuan University(grant #KS021, grant #K1907, and grant KX247), the Robert A Welch Foundation for a grant (grant #E-0004), the Swedish Cancer Foundation, the Center for Innovative Medicine and the Novo Nordisk Fund
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2020]版：
大类|2 区综合性期刊
小类|2 区综合性期刊
最新[2023]版：
大类|2 区综合性期刊
小类|2 区综合性期刊
第一作者：
第一作者机构：[1]Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE and State Key Laboratory of Biotherapy, West China Second Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, P. R. China.
共同第一作者：
通讯作者：
通讯机构：[9]Department of Biology and Biochemistry, Center for Nuclear Receptors and Cell Signaling, University of Houston, U.S.A[10]Department of Biosciences and Nutrition at NOVUM, Karolinska Institute, Sweden
推荐引用方式(GB/T 7714)：
Shuang Huang,Nianxin Zhou,Linjie Zhao,et al.Pharmacological Activation of Estrogen Receptor Beta Overcomes Tumor Resistance to Immune Checkpoint Blockade Therapy.[J].iScience.2020,23(9):101458.doi:10.1016/j.isci.2020.101458.
APA：
Shuang Huang,Nianxin Zhou,Linjie Zhao,Ryan C. Gimple,Young Ha Ahn...&Shengtao Zhou.(2020).Pharmacological Activation of Estrogen Receptor Beta Overcomes Tumor Resistance to Immune Checkpoint Blockade Therapy..iScience,23,(9)
MLA：
Shuang Huang,et al."Pharmacological Activation of Estrogen Receptor Beta Overcomes Tumor Resistance to Immune Checkpoint Blockade Therapy.".iScience 23..9(2020):101458
