文章基本信息

标题：Pharmacological Activation of Estrogen Receptor Beta Overcomes Tumor Resistance to Immune Checkpoint Blockade Therapy
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作者：Shuang Huang ; Nianxin Zhou ; Linjie Zhao 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2020
卷号：23
期号：9
页码：1-33
DOI：10.1016/j.isci.2020.101458
语种：English
出版社：Elsevier
摘要：SummaryThe 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 chemotaxisin vitroand blockade of CSF1R demonstrated similar therapeutic effects as ERβ activationin 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.Graphical AbstractDisplay OmittedHighlights•ERβ activation overcomes ICB resistance in tumors•ERβ activation and ICB therapy reduces MDSC infiltration and increases cytotoxic T cells•CSF1/CSF1R axis is suppressed in combined therapy of ERβ activation and ICB therapyImmunology; Endocrine Treatment; Cancer