Pharmacological Activation of Estrogen Receptor Beta Overcomes Tumor Resistance to Immune Checkpoint Blockade Therapy

• DOI: 10.1016/j.isci.2020.101458
• Publication Date: 2020-08-12T06:47:25Z
• Authors: Shuang Huang; Nianxin Zhou; Linjie Zhao; Ryan C. Gimple; Young Ha Ahn; Peidong Zhang; Wei Wang; Bin Shao; Jingyun Yang; Qian Zhang; Sai Zhao; Xuehan Jiang; Zhiwei Chen; Yangfan Zeng; Hongbo Hu; Jan-Åke Gustafsson; Shengtao Zhou
• Keywords: Immune checkpoint; Infiltration (HVAC); Combination therapy; Cancer Immunotherapy

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 patients with cancer, this regimen fails to extend survival large proportion patients. Here, we found that combined estrogen receptor beta (ERβ) agonist and PD-1 antibody improved therapeutic efficacy mouse tumor models, compared monotherapies, by reducing infiltration myeloid-derived suppressor cells (MDSCs) increasing CD8+ T tumors. Mechanistically, LY500307 reduced tumor-derived CSF1 decreased CSF1R+ MDSCs bed. released induced MDSC chemotaxis vitro CSF1R demonstrated similar effects as ERβ activation vivo. Collectively, our study proved enhanced response therapy.