@article{8e5359b8f7b34ed7b99212ee1c384acc,
title = "Combining TIGIT Blockade with MDSC Inhibition Hinders Breast Cancer Bone Metastasis by Activating Antitumor Immunity",
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 IL1β 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 IL1β are prominent in human bone metastasis. Our findings suggest that cotar geting immunosuppressive granulocytes and dysfunctional T cells may be a promising novel therapeutic strategy to inhibit bone metastasis.",
author = "Lea Monteran and Nour Ershaid and Ye{\textquoteright}ela Scharff and Yazeed Zoabi and Tamer Sanalla and Yunfeng Ding and Anna Pavlovsky and Yael Zait and Marva Langer and Tal Caller and Anat Eldar-Boock and Camila Avivi and Amir Sonnenblick and Ronit Satchi-Fainaro and Iris Barshack and Noam Shomron and Zhang, {Xiang H.F.} and Neta Erez",
note = "Publisher Copyright: {\textcopyright} 2024 American Association for Cancer Research.",
year = "2024",
month = jul,
day = "1",
doi = "10.1158/2159-8290.CD-23-0762",
language = "אנגלית",
volume = "14",
pages = "1252--1275",
journal = "Cancer Discovery",
issn = "2159-8274",
publisher = "American Association for Cancer Research Inc.",
number = "7",
}