T-cell immunoglobulin and mucin domain-containing protein-3 (Tim-3), an emerging immune checkpoint molecule, was found to critically regulate the pathogenesis of respiratory disorders, including chronic obstructive pulmonary disease (COPD), bronchial asthma, and bronchogenic carcinoma, through its dynamic expression patterns and genetic polymorphisms. This review synthesized current knowledge on the structural and functional characteristics of Tim-3, delineated its roles in COPD, asthma, and lung cancer, and evaluated its therapeutic potential, thereby offering novel perspectives for targeting Tim-3 in respiratory disease management.
References
[1]
McIntire, J.J., Umetsu, S.E., Akbari, O., Potter, M., Kuchroo, V.K., Barsh, G.S., et al. (2001) Identification of Tapr (An Airway Hyperreactivity Regulatory Locus) and the Linked Tim Gene Family. NatureImmunology, 2, 1109-1116. https://doi.org/10.1038/ni739
[2]
Meng, X.H., Luo, Y.J., Cui, L.Y. and Wang, S.C. (2025) Involvement of Tim-3 in Maternal-Fetal Tolerance: A Review of Current Understanding. InternationalJournalofBiologicalSciences, 21, 789-801. https://doi.org/10.7150/ijbs.106115
[3]
Das, M., Zhu, C. and Kuchroo, V.K. (2017) Tim‐3 and Its Role in Regulating Anti‐tumor Immunity. ImmunologicalReviews, 276, 97-111. https://doi.org/10.1111/imr.12520
[4]
Chinese Medical Association Allergy Branch (2022) Expert Consensus on the Mechanism and Targeted Therapy of Type 2 Inflammatory Diseases. ChineseJournalofMedicine, 102, 25.
[5]
Qiu, S.L., Zhou, G., Ke, J.Y., Zhou, J.P., Zhang, H., Jin, Z.T., etal. (2024) Impairment of Gal-9 and Tim-3 Crosstalk between Tregs and Th17 Cells Drives Tobacco Smoke‐induced Airway Inflammation. Immunology, 173, 152-171. https://doi.org/10.1111/imm.13820
[6]
Wang, Y.-X. and Zang, Y.-P. (2024) The Relationship between Serum Tim-3, Galectin-9 Levels and Acute Exacerbation and Pulmonary Function Decline in Elderly COPD Patients. ChineseJournalofGerontology, 44, 4128-4131.
[7]
Tang, X.-H., Zhang, H.-H., Wang, D.-M., et al. (2020) The Expression of Tim-3 in Peripheral Blood of Patients with Chronic Obstructive Pulmonary Disease and Its Correlation with Disease Progression. JournalofClinicalPulmonaryMedicine, 25, 4.
[8]
Boehne, C., Behrendt, A., Meyer-Bahlburg, A., Boettcher, M., Drube, S., Kamradt, T., et al. (2021) Tim-3 Is Dispensable for Allergic Inflammation and Respiratory Tolerance in Experimental Asthma. PLOSONE, 16, e0249605. https://doi.org/10.1371/journal.pone.0249605
[9]
Wu, C.-T., Lee, Y.-T., Ku, M.-S. and Lue, K.-H. (2020) Role of Biomarkers and Effect of Fip-Fve in Acute and Chronic Animal Asthma Models. JournalofMicrobiology, ImmunologyandInfection, 53, 996-1007. https://doi.org/10.1016/j.jmii.2020.07.006
[10]
Li, J.-S., Li, Q.-J, Wang, P., et al. (2006) The Correlation between Two Single Nucleotide Polymorphisms in the Promoter Region of TIM-3 Gene and Bronchial Asthma in the Han Population of Shandong, China. Journal of Shandong University (Health Science), 2006, 1159-1163.
[11]
Liang, Z.Z., Cheng, G., Meng, P., et al. (2019) Association between-574 G > T Polymorphism of TIM-3 Gene and Bronchial Asthma in Chinese Han Population: A Meta-Analysis. Chinese Journal of Lung Diseases (Electronic Edition), 12, 63-67.
[12]
Ma, J.-X., Ma C.-Q., Fan W.-W., et al. (2024) Current Status and Progress of Targeted Therapy for Non-Small Cell Lung Cancer. Journal of Shandong Second Medical University, 46, 464-470.
[13]
Qiang, F., Li, Z.Q., Ying, C., et al. (2025) Research Progress on the Antitumor Effects of Immune Checkpoint Inhibitors. The Journal of Practical Medicine, 41, 288-293.
[14]
Pagliano, O., Morrison, R.M., Chauvin, J., Banerjee, H., Davar, D., Ding, Q., etal. (2022) Tim-3 Mediates T Cell Trogocytosis to Limit Antitumor Immunity. JournalofClinicalInvestigation, 132, e152864. https://doi.org/10.1172/jci152864
[15]
Yang, R.Y., Sun, L.L., Li, C.-F., Wang, Y.-H., Yao, J., Li, H., etal. (2021) Galectin-9 Interacts with PD-1 and TIM-3 to Regulate T Cell Death and Is a Target for Cancer Immunotherapy. NatureCommunications, 12, Article No. 832. https://doi.org/10.1038/s41467-021-21099-2
[16]
D’Haens, G., Peyrin‐Biroulet, L., Marks, D.J.B., Lisi, E., Liefaard, L., Beaton, A., et al. (2023) A Randomised, Double‐Blind, Placebo‐Controlled Study of the LAG‐3‐Depleting Monoclonal Antibody GSK2831781 in Patients with Active Ulcerative Colitis. AlimentaryPharmacology&Therapeutics, 58, 283-296. https://doi.org/10.1111/apt.17557
[17]
Qiao, Y.Q., Hui, P., Dong, J.M., et al. (2022) Relationship Between Expression of TIM-3 and Prognosis, Clinicopathological Features in Non-Small Cell Lung Cancer: A Meta Analysis. InternationalJournalofRespiration, 42, 1627-1634.
[18]
Joller, N., Anderson, A.C. and Kuchroo, V.K. (2024) LAG-3, TIM-3, and TIGIT: Distinct Functions in Immune Regulation. Immunity, 57, 206-222. https://doi.org/10.1016/j.immuni.2024.01.010
[19]
Dixon, K.O., Tabaka, M., Schramm, M.A., Xiao, S., Tang, R., Dionne, D., etal. (2021) TIM-3 Restrains Anti-Tumour Immunity by Regulating Inflammasome Activation. Nature, 595, 101-106. https://doi.org/10.1038/s41586-021-03626-9
[20]
Ma, S.Y., Tian, Y., Peng, J.L., Chen, C.J., Peng, X.Q., Zhao, F.B., etal. (2023) Identification of a Small-Molecule Tim-3 Inhibitor to Potentiate T Cell-Mediated Antitumor Immunotherapy in Preclinical Mouse Models. ScienceTranslationalMedicine, 15, eadg6752. https://doi.org/10.1126/scitranslmed.adg6752
[21]
Sauer, N., Janicka, N., Szlasa, W., Skinderowicz, B., Kołodzińska, K., Dwernicka, W., et al. (2023) TIM-3 as a Promising Target for Cancer Immunotherapy in a Wide Range of Tumors. CancerImmunology, Immunotherapy, 72, 3405-3425. https://doi.org/10.1007/s00262-023-03516-1
