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 database 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 activation 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.

Key words: spermidine, breast cancer, T cells, chemotherapy

摘要： 目的 探索化疗对癌细胞亚精胺代谢的影响及其对乳腺癌免疫细胞浸润以及效应淋巴细胞激活状态的影响。方法 分析MMTV-Wnt1小鼠肿瘤细胞移植瘤化疗模型的单细胞测序数据,分析化疗后乳腺癌细胞亚精胺代谢水平改变;同时分析各亚型人乳腺癌单细胞测序,探索亚精胺代谢异质性,比较亚精胺代谢高低两组患者免疫细胞浸润和激活状态的差别。结果 MMTV-Wnt1小鼠来源肿瘤细胞移植瘤经多柔比星化疗后肿瘤细胞中富集了亚精胺代谢旺盛的亚群,该群细胞高表达亚精胺代谢相关酶ODC1、SMOX;乳腺癌细胞亚精胺代谢旺盛与效应T淋巴细胞浸润增加和CD8T淋巴细胞功能增强呈现正相关。结论 化疗促进乳腺癌细胞亚精胺代谢,肿瘤细胞亚精胺代谢活跃激活抗肿瘤免疫,从而促进肿瘤免疫。

关键词: 亚精胺, 乳腺癌, T细胞, 化疗