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Progestogen-driven B7-H4 contributes to onco-fetal immune tolerance.
Yu, Jiali; Yan, Yijian; Li, Shasha; Xu, Ying; Parolia, Abhijit; Rizvi, Syed; Wang, Weichao; Zhai, Yiwen; Xiao, Rongxin; Li, Xiong; Liao, Peng; Zhou, Jiajia; Okla, Karolina; Lin, Heng; Lin, Xun; Grove, Sara; Wei, Shuang; Vatan, Linda; Hu, Jiantao; Szumilo, Justyna; Kotarski, Jan; Freeman, Zachary T; Skala, Stephanie; Wicha, Max; Cho, Kathleen R; Chinnaiyan, Arul M; Schon, Samantha; Wen, Fei; Kryczek, Ilona; Wang, Shaomeng; Chen, Lieping; Zou, Weiping.
Afiliación
  • Yu J; Department of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, University of Michigan Rogel Cancer Center, Ann Arbor, MI, USA.
  • Yan Y; Department of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, University of Michigan Rogel Cancer Center, Ann Arbor, MI, USA.
  • Li S; Department of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, University of Michigan Rogel Cancer Center, Ann Arbor, MI, USA.
  • Xu Y; Department of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, University of Michigan Rogel Cancer Center, Ann Arbor, MI, USA.
  • Parolia A; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
  • Rizvi S; Department of Chemical Engineering, University of Michigan School of Engineering, Ann Arbor, MI, USA.
  • Wang W; Department of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, University of Michigan Rogel Cancer Center, Ann Arbor, MI, USA.
  • Zhai Y; Department of Pediatrics, University of Michigan Medical School, Ann Arbor, MI, USA.
  • Xiao R; Department of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, University of Michigan Rogel Cancer Center, Ann Arbor, MI, USA.
  • Li X; Department of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, University of Michigan Rogel Cancer Center, Ann Arbor, MI, USA.
  • Liao P; Department of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, University of Michigan Rogel Cancer Center, Ann Arbor, MI, USA.
  • Zhou J; Department of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, University of Michigan Rogel Cancer Center, Ann Arbor, MI, USA.
  • Okla K; Department of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, University of Michigan Rogel Cancer Center, Ann Arbor, MI, USA; Department of Oncological Gynecology and Gynecology, Medical University of Lublin, Lublin, P
  • Lin H; Department of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, University of Michigan Rogel Cancer Center, Ann Arbor, MI, USA.
  • Lin X; Department of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, University of Michigan Rogel Cancer Center, Ann Arbor, MI, USA.
  • Grove S; Department of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, University of Michigan Rogel Cancer Center, Ann Arbor, MI, USA.
  • Wei S; Department of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, University of Michigan Rogel Cancer Center, Ann Arbor, MI, USA.
  • Vatan L; Department of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, University of Michigan Rogel Cancer Center, Ann Arbor, MI, USA.
  • Hu J; Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
  • Szumilo J; Department of Clinical Pathomorphology, Medical University of Lublin, Lublin, Poland.
  • Kotarski J; Department of Oncological Gynecology and Gynecology, Medical University of Lublin, Lublin, Poland.
  • Freeman ZT; Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, MI, USA.
  • Skala S; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
  • Wicha M; Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
  • Cho KR; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
  • Chinnaiyan AM; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA; Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI, USA; Howard Hughes Medical Institute, University of Michigan Medical School, Ann Arbor, MI, USA.
  • Schon S; Department of Obstetrics and Gynecology, University of Michigan Medical School, Ann Arbor, MI, USA.
  • Wen F; Department of Chemical Engineering, University of Michigan School of Engineering, Ann Arbor, MI, USA.
  • Kryczek I; Department of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, University of Michigan Rogel Cancer Center, Ann Arbor, MI, USA.
  • Wang S; Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA; Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI, USA.
  • Chen L; Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.
  • Zou W; Department of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, University of Michigan Rogel Cancer Center, Ann Arbor, MI, USA; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA; Graduate
Cell ; 187(17): 4713-4732.e19, 2024 Aug 22.
Article en En | MEDLINE | ID: mdl-38968937
ABSTRACT
Immune tolerance mechanisms are shared in cancer and pregnancy. Through cross-analyzing single-cell RNA-sequencing data from multiple human cancer types and the maternal-fetal interface, we found B7-H4 (VTCN1) is an onco-fetal immune tolerance checkpoint. We showed that genetic deficiency of B7-H4 resulted in immune activation and fetal resorption in allogeneic pregnancy models. Analogously, B7-H4 contributed to MPA/DMBA-induced breast cancer progression, accompanied by CD8+ T cell exhaustion. Female hormone screening revealed that progesterone stimulated B7-H4 expression in placental and breast cancer cells. Mechanistically, progesterone receptor (PR) bound to a newly identified -58 kb enhancer, thereby mediating B7-H4 transcription via the PR-P300-BRD4 axis. PR antagonist or BRD4 degrader potentiated immunotherapy in a murine B7-H4+ breast cancer model. Thus, our work unravels a mechanistic and biological connection of a female sex hormone (progesterone) to onco-fetal immune tolerance via B7-H4 and suggests that the PR-P300-BRD4 axis is targetable for treating B7-H4+ cancer.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Progestinas / Progesterona / Inhibidor 1 de la Activación de Células T con Dominio V-Set / Tolerancia Inmunológica Límite: Animals / Female / Humans / Pregnancy Idioma: En Revista: Cell Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Progestinas / Progesterona / Inhibidor 1 de la Activación de Células T con Dominio V-Set / Tolerancia Inmunológica Límite: Animals / Female / Humans / Pregnancy Idioma: En Revista: Cell Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos