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Pituitary hormone α-MSH promotes tumor-induced myelopoiesis and immunosuppression.
Xu, Yueli; Yan, Jiaxian; Tao, Ye; Qian, Xiaojun; Zhang, Chi; Yin, Libei; Gu, Pengying; Liu, Yehai; Pan, Yueyin; Tang, Renhong; Jiang, Wei; Zhou, Rongbin.
Affiliation
  • Xu Y; Hefei National Research Center for Physical Sciences at the Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China.
  • Yan J; Hefei National Research Center for Physical Sciences at the Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China.
  • Tao Y; Department of Otolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
  • Qian X; Department of Oncology, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China.
  • Zhang C; Hefei National Research Center for Physical Sciences at the Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China.
  • Yin L; Hefei National Research Center for Physical Sciences at the Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China.
  • Gu P; Department of Geriatrics, Gerontology Institute of Anhui Province, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China.
  • Liu Y; Department of Otolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
  • Pan Y; Department of Oncology, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China.
  • Tang R; State Key Laboratory of Translational Medicine and Innovative Drug Development, Nanjing 21000, China.
  • Jiang W; Hefei National Research Center for Physical Sciences at the Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China.
  • Zhou R; Hefei National Research Center for Physical Sciences at the Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China.
Science ; 377(6610): 1085-1091, 2022 09 02.
Article in En | MEDLINE | ID: mdl-35926007
ABSTRACT
The hypothalamic-pituitary (HP) unit can produce various hormones to regulate immune responses, and some of its downstream hormones or effectors are elevated in cancer patients. We show that the HP unit can promote myelopoiesis and immunosuppression to accelerate tumor growth. Subcutaneous implantation of tumors induced hypothalamus activation and pituitary α-melanocyte-stimulating hormone (α-MSH) production in mice. α-MSH acted on bone marrow progenitors to promote myelopoiesis, myeloid cell accumulation, immunosuppression, and tumor growth through its melanocortin receptor MC5R. MC5R peptide antagonist boosted antitumor immunity and anti-programmed cell death protein 1 (anti-PD-1) immunotherapy. Serum α-MSH concentration was elevated and correlated with circulating myeloid-derived suppressor cells in cancer patients. Our results reveal a neuroendocrine pathway that suppresses tumor immunity and suggest MC5R as a potential target for cancer immunotherapy.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Alpha-MSH / Myelopoiesis / Hypothalamo-Hypophyseal System / Immune Tolerance / Neoplasms Limits: Animals Language: En Journal: Science Year: 2022 Document type: Article
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Alpha-MSH / Myelopoiesis / Hypothalamo-Hypophyseal System / Immune Tolerance / Neoplasms Limits: Animals Language: En Journal: Science Year: 2022 Document type: Article