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Combining TIGIT Blockade with MDSC Inhibition Hinders Breast Cancer Bone Metastasis by Activating Antitumor Immunity.
Monteran, Lea; Ershaid, Nour; Scharff, Ye'ela; Zoabi, Yazeed; Sanalla, Tamer; Ding, Yunfeng; Pavlovsky, Anna; Zait, Yael; Langer, Marva; Caller, Tal; Eldar-Boock, Anat; Avivi, Camila; Sonnenblick, Amir; Satchi-Fainaro, Ronit; Barshack, Iris; Shomron, Noam; Zhang, Xiang H-F; Erez, Neta.
Afiliación
  • Monteran L; Department of Pathology, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
  • Ershaid N; Department of Pathology, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
  • Scharff Y; Department of Pathology, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
  • Zoabi Y; Department of Cell and Developmental Biology, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
  • Sanalla T; Department of Pathology, Sheba Medical Center, Tel Hashomer, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
  • Ding Y; Lester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, Texas.
  • Pavlovsky A; Department of Pathology, Sheba Medical Center, Tel Hashomer, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
  • Zait Y; Department of Pathology, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
  • Langer M; Department of Pathology, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
  • Caller T; Tamman Cardiovascular Research Institute, Sheba Medical Center, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
  • Eldar-Boock A; Department of Physiology and Pharmacology, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
  • Avivi C; Department of Pathology, Sheba Medical Center, Tel Hashomer, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
  • Sonnenblick A; Oncology Division, Tel Aviv Sourasky Medical Center, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
  • Satchi-Fainaro R; Department of Physiology and Pharmacology, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
  • Barshack I; Department of Pathology, Sheba Medical Center, Tel Hashomer, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
  • Shomron N; Department of Cell and Developmental Biology, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
  • Zhang XH; Lester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, Texas.
  • Erez N; Department of Pathology, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Cancer Discov ; 14(7): 1252-1275, 2024 Jul 01.
Article en En | MEDLINE | ID: mdl-38427556
ABSTRACT
Bone is the most common site of breast cancer metastasis. Bone metastasis is incurable and is associated with severe morbidity. Utilizing an immunocompetent mouse model of spontaneous breast cancer bone metastasis, we profiled the immune transcriptome of bone metastatic lesions and peripheral bone marrow at distinct metastatic stages, revealing dynamic changes during the metastatic process. We show that cross-talk between granulocytes and T cells is central to shaping an immunosuppressive microenvironment. Specifically, we identified the PD-1 and TIGIT signaling axes and the proinflammatory cytokine IL1ß as central players in the interactions between granulocytes and T cells. Targeting these pathways in vivo resulted in attenuated bone metastasis and improved survival, by reactivating antitumor immunity. Analysis of patient samples revealed that TIGIT and IL1ß are prominent in human bone metastasis. Our findings suggest that cotargeting immunosuppressive granulocytes and dysfunctional T cells may be a promising novel therapeutic strategy to inhibit bone metastasis.

Significance:

Temporal transcriptome profiling of the immune microenvironment in breast cancer bone metastasis revealed key communication pathways between dysfunctional T cells and myeloid derived suppressor cells. Cotargeting of TIGIT and IL1ß inhibited bone metastasis and improved survival. Validation in patient data implicated these targets as a novel promising approach to treat human bone metastasis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Óseas / Neoplasias de la Mama / Receptores Inmunológicos / Células Supresoras de Origen Mieloide Límite: Animals / Female / Humans Idioma: En Revista: Cancer Discov Año: 2024 Tipo del documento: Article País de afiliación: Israel Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Óseas / Neoplasias de la Mama / Receptores Inmunológicos / Células Supresoras de Origen Mieloide Límite: Animals / Female / Humans Idioma: En Revista: Cancer Discov Año: 2024 Tipo del documento: Article País de afiliación: Israel Pais de publicación: Estados Unidos