← 返回

TIM-1 在肺腺癌患者中的分布特征及预后价值

英文原题:Distribution characteristics and prognostic value of TIM-1 in patients with lung adenocarcinoma.

查看英文原题

Distribution characteristics and prognostic value of TIM-1 in patients with lung adenocarcinoma.

PubMed 2025/05/30(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。

研究概要

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 细胞密度来发挥免疫抑制。这些发现突显了 TIM-1+B 细胞作为潜在治疗靶点的重要性。

研究思路结论见上方概要

T细胞免疫球蛋白和黏蛋白结构域蛋白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)中的确切作用和分布特征仍是关键的研究领域。

本研究对126例肺腺癌(LUAD)患者的组织切片进行了多重免疫荧光(mIF)检测,以探讨TIM-1的分布模式以及三种TIM-1阳性免疫细胞群在原发肿瘤和肿瘤引流淋巴结(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)相关(mOS,84 vs. 54个月;p<0.0001,HR=2.574)和无病生存期(DFS)(mDFS,53.0 vs. 23.1个月;p=0.018,HR=1.721)。在TDLN中,较低的TIM-1+B细胞密度也与更长的OS相关(mOS,未达到 vs. 64.7个月;p=0.0019,HR=2.3502)和DFS(mDFS,68.5 vs. 28.9个月;p=0.016,HR=1.707)。TDLN中较高的TIM-1+B细胞密度与较低比例的成熟三级淋巴结构(TLS)相关(p=0.0009,r=-0.3990),并且肿瘤中TIM-1+B细胞密度的增加与CD8+T细胞密度降低相关(p=0.016,r=-0.2788)。

展开英文摘要原文

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.

论文信息

作者
Wen J、Yun W、Chen Y、Yin X、Cui W、Yu M、Meng X
单位
Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.China
期刊
Frontiers in immunology2025
原文标识
PubMed 40519901 · DOI 10.3389/fimmu.2025.1602868