Activation of G protein-coupled estrogen receptor signaling inhibits melanoma and improves response to immune checkpoint blockade.
作者： Christopher A Natale , Jinyang Li , Junqian Zhang , Ankit Dahal , Tzvete Dentchev
DOI: 10.7554/ELIFE.31770
关键词: Cancer research 、 Immune checkpoint 、 Estrogen receptor 、 Immunotherapy 、 Melanoma 、 Melanocyte differentiation 、 Medicine 、 Cellular differentiation 、 GPER 、 Blockade
摘要: Female sex and history of prior pregnancies are associated with favorable melanoma outcomes. Here, we show that much the protective effect likely results from estrogen signaling through G protein-coupled receptor (GPER) on melanocytes. Selective GPER activation in primary melanocytes cells induced long-term changes maintained a more differentiated cell state as defined by increased expression well-established melanocyte differentiation antigens, pigment production, decreased proliferative capacity, oncodriver stem marker c-Myc. also rendered vulnerable to immunotherapy. Systemically delivered agonist was well tolerated, cooperated immune checkpoint blockade melanoma-bearing mice dramatically extend survival, up half clearing their tumor. Complete responses were memory protected against tumor rechallenge. may be useful, pharmacologically accessible target for melanoma.
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