提吉特
骨髓
转移
癌症研究
乳腺癌
癌症
医学
肿瘤微环境
骨转移
细胞因子
免疫系统
免疫学
免疫疗法
内科学
作者
Lea Monteran,Nour Ershaid,Ye’ela Scharff,Yazeed Zoabi,Tamer Sanalla,Yunfeng Ding,A J Pavlovsky,Yael Zait,Marva Langer,Tal Caller,Anat Eldar‐Boock,Camila Avivi,Amir Sonnenblick,Ronit Satchi‐Fainaro,Iris Barshack,Noam Shomron,Xiang H.-F. Zhang,Neta Erez
出处
期刊:Cancer Discovery
[American Association for Cancer Research]
日期:2024-03-01
标识
DOI:10.1158/2159-8290.cd-23-0762
摘要
Bone is the most common site of breast cancer metastasis. Bone metastasis are incurable and are 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 crosstalk between granulocytes and T cells is central to shaping an immunosuppressive microenvironment. Specifically, we identified the PD-1 and TIGIT signaling axes and the pro-inflammatory cytokine IL1b 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 anti-tumor immunity. Analysis of patient samples revealed that TIGIT and IL1b are prominent in human bone metastasis. Our findings suggest that co-targeting immunosuppressive granulocytes and dysfunctional T cells may be a promising novel therapeutic strategy to inhibit bone metastasis.
科研通智能强力驱动
Strongly Powered by AbleSci AI