虽然已被公认为YTH N6-甲基腺苷酸RNA结合蛋白1（YTHDF1）是多种肿瘤发展和免疫相关调节的重要因子，但其在乳腺癌免疫反应中的功能主要未受到研究。通过对公共数据库的分析，我们发现YTHDF1在乳腺癌中是高表达的基因，并在我们中心的乳腺癌细胞和临床样本中证实了这一发现。随后，我们利用免疫相关的公共数据库和算法，研究了YTHDF1表达与免疫细胞和分子之间的联系。我们通过细胞和动物实验以及RNA测序验证了我们的发现。发现YTHDF1在乳腺癌肿瘤组织中高表达，与患者生存率呈负相关。降低YTHDF1促进了炎性标记物的表达，并提高了乳腺癌免疫细胞的抗癌能力。RNA测序分析显示，YTHDF1沉默导致信号转导途径中差异基因的富集。此外，体外实验证明，免疫细胞对YTHDF1表达下调的乳腺癌细胞具有更高的细胞毒性。此外，体内研究表明，YTHDF1促进乳腺癌生长，同时抑制CD8+ T细胞浸润和功能。我们的研究表明，YTHDF1通过抑制癌细胞释放炎性因子，对乳腺癌的"冷"肿瘤微环境起着至关重要的作用。因此，抗肿瘤CD8+ T细胞的浸润和功能分化受到阻碍，最终导致乳腺癌的免疫逃逸。版权所有 © 2023. Elsevier Inc. 发表。

While YTH N6-methyladenosine RNA binding protein 1 (YTHDF1) was recognized as a crucial contributor in the development and immune-related regulation of various types of tumors, its function in the immune response of breast cancer has largely remained uninvestigated. Through analysis of public databases, we found YTHDF1 as a highly expressed gene in breast cancers and confirmed this finding in breast cancer cells and clinical specimens from our center. Subsequently, we examined the link between YTHDF1 expression and immune cells and molecules by utilizing immune-related public databases and algorithm. We further validated our findings through cellular and animal experiments, as well as RNA sequencing. YTHDF1 was found highly expressed in tumor tissues of breast cancer, which negatively correlated with patient survival. The downregulation of YTHDF1 promoted the expression of pro-inflammatory markers and improved the anti-cancer ability of immune cells in breast cancer. RNA sequencing analysis revealed that YTHDF1 knockdown resulted in enrichment of differential genes in signal transduction pathways. Additionally, in vitro experiments showed that immune cells had higher cytotoxicity against breast cancer cells with decreased YTHDF1 expression. Moreover, in vivo studies indicated that YTHDF1 promoted breast cancer growth while inhibiting CD8+ T cell infiltration and function. Our study demonstrates that YTHDF1 plays a crucial role in establishing a "cold" tumor microenvironment in breast cancer by inhibiting the release of pro-inflammatory cytokines from cancer cells. As a result, the infiltration and functional differentiation of anti-tumor CD8+ T cells are hindered, ultimately resulting in the immune evasion of breast cancer.Copyright © 2023. Published by Elsevier Inc.