ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1602868
This article is part of the Research TopicLung Adenocarcinoma: From Genomics to Immunotherapy, Volume IIView all 16 articles
Distribution characteristics and prognostic value of TIM-1 in patients with lung adenocarcinoma
Provisionally accepted
- Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong First Medical University, Jinan, China
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Background 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.Methods 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.
Keywords: TIM-1, T-cell immunoglobulin and mucin domaincontaining protein 1, TME, tumor microenvironment, mIF, multiplex immunofluorescence, TDLN, tumor-draining lymph nodes, OS, overall survival, DFS, disease-free survival, TLS, tertiary lymphoid structure, ICB, immune checkpoint blockade
Received: 30 Mar 2025; Accepted: 13 May 2025.
Copyright: © 2025 Wen, Yun, Chen, Yin, Cui, Yu and Meng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Xiangjiao Meng, Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong First Medical University, Jinan, China
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