T细胞免疫球蛋白黏蛋白3高表达促进单核细胞迁移预测非小细胞肺癌预后

周璐1 陈思通 李春燕 黄燕燕 续力云

解剖学报 ›› 2025, Vol. 56 ›› Issue (6) : 697-703.

PDF(4565 KB)
欢迎访问《解剖学报》官方网站!今天是 English
PDF(4565 KB)
解剖学报 ›› 2025, Vol. 56 ›› Issue (6) : 697-703. DOI: 10.16098/j.issn.0529-1356.2025.06.009
肿瘤生物学

T细胞免疫球蛋白黏蛋白3高表达促进单核细胞迁移预测非小细胞肺癌预后

  • 周璐1 陈思通2 李春燕3 黄燕燕3 续力云1* 
作者信息 +

High expression of T-cell immunoglobulin and mucin domain-containing protein 3 predicting prognosis of non-small cell lung cancer by promoting monocyte migration

  • ZHOU  Lu1  CHEN  Si-tong2  LI  Chun-yan3  HUANG  Yan-yan3  XU  Li-yun1,3* 
Author information +
文章历史 +

摘要

目的 探讨T细胞免疫球蛋白黏蛋白3(TIM-3)在外周血单核细胞中的表达,及其与非小细胞肺癌(NSCLC)之间的关系。    方法 采用流式细胞术分析116例NSCLC患者和37例健康志愿者外周血单核细胞TIM-3表达。多重免疫组织化学检测组织巨噬细胞TIM-3的表达。细胞迁移实验检测单核细胞迁移能力。采用Real-time PCR和ELISA检测单核细胞TIM-3 mRNA和蛋白表达。    结果 与健康志愿者相比,NSCLC患者外周血单核细胞TIM-3表达上调(P<0.05)。NSCLC患者TIM-3主要在癌旁组织巨噬细胞表达,与单核细胞表达成正相关(P<0.05)。TIM-3高表达促进NSCLC患者单核细胞迁移(P<0.05),外周血单核细胞TIM-3高表达预示预后不良(P<0.05)。    结论 外周血单核细胞TIM-3表达可能是预测NSCLC患者预后的一个有用指标,TIM-3可能成为免疫治疗策略的新靶点。

Abstract

Objective To investigate the expression of T cell immunoglobulin and mucin domaincontaining protein 3 (TIM-3) in peripheral blood mononuclear cells and its relationship with non-small cell lung cancer (NSCLC).    Methods TIM-3 expression in monocytes from the peripheral blood of 116 NSCLC patients and 37 healthy volunteers was analyzed via flow cytometry. The expression of TIM-3 in macrophages from tissues was detected via multiplex immunohistochemical staining. Transwell migration experiments were used to detect the migration ability of monocytes. Real-time PCR and ELISA were used to detect the mRNA and protein expression of TIM-3 in monocytes.    Results Compared with that in healthy volunteers, TIM-3 expression was upregulated in the peripheral blood monocytes of NSCLC patients (P<0.05). TIM-3 was expressed mainly in macrophages in adjacent tissues and positively correlated with its expression in monocytes in NSCLC patients (P<0.05). Furthermore, high TIM-3 expression promoted monocyte migration in NSCLC patients (P<0.05), and high TIM-3 expression in peripheral blood monocytes indicated poor prognosis(P<0.05).    Conclusion TIM-3 expression in peripheral blood monocytes may be a useful indicator of the disease prognosis of NSCLC patients and TIM-3 could be a new target for immunotherapeutic strategies. 

关键词

T细胞免疫球蛋白黏蛋白3 / 单核细胞 / 迁移能力 / 非小细胞肺癌 / 预后 / 流式细胞术 /

Key words

T cell immunoglobulin and mucin domain-containing protein 3
/ Monocyte / Migration ability / Non-small cell lung cancer / Prognosis / Flow cytometry / Human

引用本文

导出引用
周璐1 陈思通 李春燕 黄燕燕 续力云. T细胞免疫球蛋白黏蛋白3高表达促进单核细胞迁移预测非小细胞肺癌预后[J]. 解剖学报. 2025, 56(6): 697-703 https://doi.org/10.16098/j.issn.0529-1356.2025.06.009
ZHOU Lu CHEN Si-tong LI Chun-yan HUANG Yan-yan XU Li-yun.
High expression of T-cell immunoglobulin and mucin domain-containing protein 3 predicting prognosis of non-small cell lung cancer by promoting monocyte migration
[J]. Acta Anatomica Sinica. 2025, 56(6): 697-703 https://doi.org/10.16098/j.issn.0529-1356.2025.06.009
中图分类号: R329.2   

参考文献

 [1] Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2018, 68(6):394-424.
 [2] Kwiecień I, Rutkowska E, Polubiec-Kownacka M,et al. Blood monocyte subsets with activation markers in relation with macrophages in nonsmall cell lung cancer[J]. Cancers (Basel), 2020, 12(9):2513.
 [3] Wang L, Mei X, Liu X, et al. The interleukin-33/ST2 axis enhances lung-resident CD14+ monocyte function in patients with non-small cell lung cancer[J]. Immunol Invest, 2023, 52(1):67-82.
 [4] Qian B Z, Li J, Zhang H, et al. CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis[J]. Nature, 2011, 475(7355):222-225.
 [5] Hanna RN, Cekic C, Sag D, et al. Patrolling monocytes control tumor metastasis to the lung[J]. Science, 2015, 350(6263):985-990.
 [6] Monney L, Sabatos CA, Gaglia JL, et al. Th1-specific cell surface protein Tim-3 regulates macrophage activation and severity of an autoimmune disease[J]. Nature, 2002, 415(6871):536-541.
 [7] Ausejo-Mauleon I, Labiano S, De La Nava D, et al. TIM-3 blockade in diffuse intrinsic pontine glioma models promotes tumor regression and antitumor immune memory[J]. Cancer Cell, 2023, 41(11):1911-1926.
 [8] Zhuang X, Zhang X, Xia X, et al. Ectopic expression of TIM-3 in lung cancers: a potential independent prognostic factor for patients with NSCLC[J]. Am J Clin Pathol, 2012, 137(6):978-985.
 [9] Shi Y, Wu W, Yang Y, et al. Decreased Tim-3 expression is associated with functional abnormalities of monocytes in decompensated cirrhosis without overt bacterial infection[J]. J Hepatol, 2015, 63(1):60-67.
 [10] Das M, Zhu C, Kuchroo VK. Tim-3 and its role in regulating anti-tumor immunity[J]. Immunol Rev, 2017, 276(1):97-111.
 [11] Acharya N, Sabatos-Peyton C, Anderson AC. Tim-3 finds its place in the cancer immunotherapy landscape[J]. J Immunother Cancer, 2020, 8(1):e000911.
 [12] Datar I, Sanmamed MF, Wang J, et al. Expression analysis and significance of PD-1, LAG-3, and TIM-3 in human non-small cell lung cancer using spatially resolved and multiparametric single-cell analysis[J]. Clin Cancer Res, 2019, 25(15):4663-4673.
 [13] Guégan J P, Peyraud F, DadoneMontaudie B, et al. Analysis of PD1, LAG3, TIGIT, and TIM3 expression in human lung adenocarcinoma reveals a 25-gene signature predicting immunotherapy response[J]. Cell Rep Med, 2024, 5(12):101831.
 [14] Cassetta L, Fragkogianni S, Sims AH, et al. Human tumor-associated macrophage and monocyte transcriptional landscapes reveal cancer-specific reprogramming, biomarkers, and therapeutic targets[J]. Cancer Cell, 2019, 35(4):588-602.
 [15] Guo Q, Shen S, Guan G, et al. Cancer cell intrinsic TIM-3 induces glioblastoma progression[J]. iScience, 2022, 25(11):105329.
 [16] He X, Peng Y, He G, et al. Increased co-expression of PD1 and TIM3 is associated with poor prognosis and immune microenvironment heterogeneity in gallbladder cancer[J]. J Transl Med, 2023, 21(1):717.
 [17] Chen K, Gu Y, Cao Y, et al. TIM3(+) cells in gastric cancer: clinical correlates and association with immune context[J]. Br J Cancer, 2022, 126(1):100-108.
 [18] Palacios L M, Peyret V, Viano ME, et al. TIM3 expression in anaplastic-thyroid-cancer-infiltrating macrophages: An emerging immunotherapeutic target[J]. Biology (Basel), 2022, 11(11):1609.
 [19] Khademi M, Illés Z, Gielen AW, et al. T Cell Ig- and mucin-domain-containing molecule-3 (TIM-3) and TIM-1 molecules are differentially expressed on human Th1 and Th2 cells and in cerebrospinal fluid-derived mononuclear cells in multiple sclerosis[J]. J Immunol, 2004, 172(11):7169-7176.
 [20] Xu L, Huang Y, Tan L, et al. Increased Tim-3 expression in peripheral NK cells predicts a poorer prognosis and Tim-3 blockade improves NK cell-mediated cytotoxicity in human lung adenocarcinoma[J]. Int Immunopharmacol, 2015, 29(2):635-641.

基金

浙江省医药卫生重点项目(WKJ-ZJ-2451);浙江省医药卫生一般项目(2025KY1798);舟山市医药卫生科技计划项目(2024YA01)

PDF(4565 KB)

Accesses

Citation

Detail

段落导航
相关文章

/