肿瘤微环境
免疫疗法
癌症研究
免疫系统
间质细胞
免疫检查点
转移
FOXP3型
医学
提吉特
癌细胞
癌症
细胞毒性T细胞
乳腺癌
免疫学
生物
内科学
体外
生物化学
作者
Yutian Zou,Feng Ye,Yanan Kong,Xiaoqian Hu,Xinpei Deng,Jindong Xie,Cailu Song,Xueqi Ou,Song Wu,Linyu Wu,Yi Xie,W. H. Tian,Yuhui Tang,Chau‐Wei Wong,Zhe‐Sheng Chen,Xinhua Xie,Hailin Tang
标识
DOI:10.1002/advs.202203699
摘要
Abstract Distant metastasis remains the major cause of morbidity for breast cancer. Individuals with liver or brain metastasis have an extremely poor prognosis and low response rates to anti‐PD‐1/L1 immune checkpoint therapy compared to those with metastasis at other sites. Therefore, it is urgent to investigate the underlying mechanism of anti‐PD‐1/L1 resistance and develop more effective immunotherapy strategies for these patients. Using single‐cell RNA sequencing, a high‐resolution map of the entire tumor ecosystem based on 44 473 cells from breast cancer liver and brain metastases is depicted. Identified by canonical markers and confirmed by multiplex immunofluorescent staining, the metastatic ecosystem features remarkable reprogramming of immunosuppressive cells such as FOXP3+ regulatory T cells, LAMP3+ tolerogenic dendritic cells, CCL18+ M2‐like macrophages, RGS5+ cancer‐associated fibroblasts, and LGALS1+ microglial cells. In addition, PD‐1 and PD‐L1/2 are barely expressed in CD8+ T cells and cancer/immune/stromal cells, respectively. Interactions of the immune checkpoint molecules LAG3‐LGALS3 and TIGIT‐NECTIN2 between CD8+ T cells and cancer/immune/stromal cells are found to play dominant roles in the immune escape. In summary, this study dissects the intratumoral heterogeneity and immunosuppressive microenvironment in liver and brain metastases of breast cancer for the first time, providing insights into the most appropriate immunotherapy strategies for these patients.
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