生物
癌症研究
免疫系统
肿瘤微环境
乳腺癌
化疗
CD8型
T细胞
免疫检查点
癌症
内科学
免疫学
免疫疗法
医学
遗传学
作者
Fang Jia,Shanshan Sun,Jiaxin Li,W Wang,Huanhuan Huang,Xiaoxiao Hu,Sheng Pan,Wuzhen Chen,Lianfang Shen,Yao Yao,Siwei Zheng,Hailong Chen,Wenjie Xia,Hongjun Yuan,Jun Zhou,Xijie Yu,Ting Zhang,Bing Zhang,Jian Huang,Chao Ni
标识
DOI:10.1016/j.canlet.2024.216656
摘要
Hormone receptor-positive breast cancer (HR + BC) is known to be relatively insensitive to chemotherapy, and since chemotherapy has remained the major neoadjuvant therapy for HR + BC, the undetermined mechanism of chemoresistance and how chemotherapy reshapes the immune microenvironment need to be explored by high-throughput technology. By using single-cell RNA sequencing and multiplexed immunofluorescence staining analysis of HR + BC samples (paired pre- and post-neoadjuvant chemotherapy (NAC)), the levels of previously unrecognized immune cell subsets, including CD8+ T cells with pronounced expression of T-cell development (LMNA) and cytotoxicity (FGFBP2) markers, CD4+ T cells characterized by proliferation marker (ATP1B3) expression and macrophages characterized by CD52 expression, were found to be increased post-NAC, which were predictive of chemosensitivity and their antitumor function was also validated with in vitro experiments. In terms of immune checkpoint expression of CD8+ T cells, we found their changes were inconsistent post-NAC, that LAG3, VSIR were decreased, and PDCD1, HAVCR2, CTLA4, KLRC1 and BTLA were increased. In addition, we have identified novel genomic and transcriptional patterns of chemoresistant cancer cells, both innate and acquired, and have confirmed their prognostic value with TCGA cohorts. By shedding light on the ecosystem of HR + BC reshaped by chemotherapy, our results uncover valuable candidates for predicting chemosensitivity and overcoming chemoresistance in HR + BC.
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