Wen Junxu, Yun Wenhua, Chen Yu, Yin Xiaoyan, Cui Wenxing, Yu Minghao, Meng Xiangjiao
Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
Front Immunol. 2025 May 30;16:1602868. doi: 10.3389/fimmu.2025.1602868. eCollection 2025.
T-cell immunoglobulin and mucin domain-containing protein 1 (TIM-1) has been identified as a promoter of tumor cell viability, migration, and invasion. However, the precise role and distribution characteristics of TIM-1 within the tumor microenvironment (TME) remain critical areas of investigation.
In this study, multiplex immunofluorescence (mIF) was performed on tissue slides from 126 patients with lung adenocarcinoma (LUAD) to investigate the distribution patterns of TIM-1 and the prognostic significance of three TIM-1 positive immune cell populations in both the primary tumor and tumor-draining lymph nodes (TDLN).
Compared to the primary tumor, TIM-1+CD8+T cells and TIM-1+B cells exhibited significantly greater density in the TDLN (p<0.0001, p<0.0001 respectively). In the primary tumor, lower TIM-1+B cell density was associated with longer overall survival (OS) (mOS, 84 vs. 54 months; p<0.0001, HR=2.574) and disease-free survival (DFS) (mDFS, 53.0 vs. 23.1 months; p=0.018, HR=1.721). In the TDLN, lower TIM-1+B cell density was also correlated with longer OS (mOS, not reached vs. 64.7 months; p=0.0019, HR=2.3502) and DFS (mDFS, 68.5 vs. 28.9 months; p=0.016, HR=1.707). Higher TIM-1+B cell density in the TDLN was associated with a lower proportion of mature tertiary lymphoid structures (TLS) (p=0.0009, r=-0.3990) and increased density of TIM-1+B cells in the tumor was linked to reduced CD8+ T cell density (p=0.016, r=-0.2788).
Our findings confirm the immunosuppressive role of TIM-1+B cells in LUAD and suggest that TIM-1+B cells exert immune suppression by inhibiting TLS maturation and CD8+ T cell density. These findings highlight TIM-1+ B cells as a potential therapeutic target.
含T细胞免疫球蛋白和粘蛋白结构域蛋白1（TIM-1）已被确定为肿瘤细胞活力、迁移和侵袭的促进因子。然而，TIM-1在肿瘤微环境（TME）中的精确作用和分布特征仍是关键的研究领域。
在本研究中，对126例肺腺癌（LUAD）患者的组织切片进行多重免疫荧光（mIF）检测，以研究TIM-1的分布模式以及三种TIM-1阳性免疫细胞群体在原发性肿瘤和引流肿瘤淋巴结（TDLN）中的预后意义。
与原发性肿瘤相比，TIM-1+CD8+T细胞和TIM-1+B细胞在TDLN中的密度显著更高（分别为p<0.0001，p<0.0001）。在原发性肿瘤中，较低的TIM-1+B细胞密度与更长的总生存期（OS）（中位总生存期，84个月对54个月；p<0.0001，HR=2.574）和无病生存期（DFS）（中位无病生存期，53.0个月对23.1个月；p=0.018，HR=1.721）相关。在TDLN中，较低的TIM-1+B细胞密度也与更长的OS（中位总生存期，未达到对64.7个月；p=0.0019，HR=2.3502）和DFS（中位无病生存期，68.5个月对28.9个月；p=0.016，HR=1.707）相关。TDLN中较高的TIM-1+B细胞密度与成熟三级淋巴结构（TLS）的比例较低相关（p=0.0009，r=-0.3990），且肿瘤中TIM-1+B细胞密度增加与CD8+T细胞密度降低相关（p=0.016，r=-0.2788）。
我们的研究结果证实了TIM-1+B细胞在LUAD中的免疫抑制作用，并表明TIM-1+B细胞通过抑制TLS成熟和CD8+T细胞密度发挥免疫抑制作用。这些发现突出了TIM-1+B细胞作为潜在治疗靶点的地位。
