岭南现代临床外科2023,Vol.23Issue(5):379-386,8.DOI:10.3969/j.issn.1009-976X.2023.05.002
单细胞转录组测序揭示化疗增强乳腺癌细胞亚精胺代谢激活肿瘤免疫
Single-cell profiling reveals that chemotherapy potentiates antitumor immunity in breast cancer through spermidine metabolism modulation
摘要
Abstract
Objective To explore the alterations of spermidine metabolism in breast cancer in response to chemotherapy,and the subsequent impact on immune cell infiltration and lymphocytic activation.Methods The single-cell RNA sequencing data of MMTV-Wnt1 tumor transplants from the online data-base were re-analyzed to identify the adjustments of spermidine metabolism in breast cancer cells after chemotherapy.Additionally,investigations were performed on the single-cell RNA-Seq data on multiple breast samples of various subtypes from GEO:GSE176078 to uncover the heterogeneity of spermidine metabolism in cancer cells.Based on the expression of genes associated with spermidine metabolism,breast cancer samples were divided into two categories:the high-spermidine-metabolism group and the low-spermidine-metabolism group.Then the variations in immune cell infiltration and lymphocytic activa-tion were further evaluated between the two groups.Results A subpopulation of tumor cells with active spermidine metabolism and high levels of ODC1 and SMOX expression,the enzymes related to spermidine metabolism,were significantly enriched in the transplant tumors after chemotherapy with doxorubicin.Moreover,active spermidine metabolism in cancer cells was positively correlated with increased effector T-cell infiltration and enhanced CD8 T-cell functions in breast cancer.Conclusion Chemotherapy potentiated antitumor immunity in breast cancer by activating the spermidine metabolism.关键词
亚精胺/乳腺癌/T细胞/化疗Key words
spermidine/breast cancer/T cells/chemotherapy分类
医药卫生引用本文复制引用
刘子菲,黄鹏翰,江咏雪,曾文锋..单细胞转录组测序揭示化疗增强乳腺癌细胞亚精胺代谢激活肿瘤免疫[J].岭南现代临床外科,2023,23(5):379-386,8.基金项目
广东省海洋经济发展(海洋六大产业)专项资金(粤自然资合[2021]51号) (海洋六大产业)