Song Kyung-Hee, Jung Seung-Youn, Park Jeong-In, Lee Dong-Hyeon, Ahn Jiyeon, Hwang Sang-Gu, Song Jie-Young
Division of Radiation Biomedical Research, Korea Institute of Radiological & Medical Sciences, 75 nowon-ro, nowon-gu, Seoul, 01812, Republic of Korea.
Sci Rep. 2025 Aug 25;15(1):31247. doi: 10.1038/s41598-025-17322-5.
Signaling lymphocytic activation molecule (SLAM) family receptors are widely expressed on immune cells, often acting as self-ligands and playing crucial roles in cellular communication and adhesion, thereby modulating immune responses. Several studies have demonstrated that SLAM family receptors are associated with potential immune checkpoints on T cells and play a role in tumor immunity in various cancers. However, the effect of SLAMF1 expression in tumors has been rarely investigated. Here, we confirmed SLAMF1 expression using tissue microarray analysis in breast cancer tissues with diverse pathological characteristics and subtypes. Additionally, SLAMF1 expression in triple-negative breast cancer (TNBC) cells was analyzed using flow cytometry and real-time PCR. Public clinical data analysis suggests that a positive correlation exists between SLAMF1 expression and overall survival and that SLAMF1 levels are slightly increased in patients with breast cancer who received radiation therapy. Similarly, when TNBC cells were irradiated, SLAMF1 expression specifically increased compared to that in non-irradiated cells. To study the biological function of SLAMF1 in mice, we established 4T1-SLAMF1 overexpressing a stable cell line. In the 4T1 syngenetic tumor model, SLAMF1 overexpression triggered strong infiltrating-CD8+ T cell responses and significantly reduced the tumor growth. Our results provide clear evidence for SLAMF1 expression in breast cancer and provide insights into the recent advances in SLAM-based targeted immunotherapies.
信号淋巴细胞激活分子(SLAM)家族受体在免疫细胞上广泛表达,常作为自身配体,在细胞通讯和黏附中发挥关键作用,从而调节免疫反应。多项研究表明,SLAM家族受体与T细胞上潜在的免疫检查点相关,并在多种癌症的肿瘤免疫中发挥作用。然而,SLAMF1在肿瘤中的表达影响鲜有研究。在此,我们通过组织微阵列分析,在具有不同病理特征和亚型的乳腺癌组织中证实了SLAMF1的表达。此外,使用流式细胞术和实时PCR分析了三阴性乳腺癌(TNBC)细胞中SLAMF1的表达。公开临床数据分析表明,SLAMF1表达与总生存期呈正相关,且接受放射治疗的乳腺癌患者中SLAMF1水平略有升高。同样,当TNBC细胞受到辐射时,与未受辐射的细胞相比,SLAMF1表达特异性增加。为了研究SLAMF1在小鼠中的生物学功能,我们建立了过表达稳定细胞系的4T1-SLAMF1。在4T1同基因肿瘤模型中,SLAMF1过表达引发强烈的浸润性CD8 + T细胞反应,并显著降低肿瘤生长。我们的结果为SLAMF1在乳腺癌中的表达提供了明确证据,并为基于SLAM的靶向免疫疗法的最新进展提供了见解。