| Citation: |
ZHOU Shimeng, LI Mengmeng, WANG Shouyu. Major Vault Protein in Macrophages Reprograms Immune Microenvironment and Inhibits Occurrence and Development of Liver Cancer[J]. Cancer Research on Prevention and Treatment, 2025, 52(2): 118-126. DOI: 10.3971/j.issn.1000-8578.2025.24.0784
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To explore the role and molecular mechanism of major vault protein (MVP) in tumor-associated macrophages in the occurrence and development of liver cancer.
The expression of MVP in macrophages was analyzed by bioinformatics method and multi-fluorescent immunohistochemical staining. Mice with MVP deficiency in macrophages were constructed by Cre/LoxP recombinant enzyme system. The proliferation and migration abilities of tumor cells were detected by cloning formation and Transwell migration assays. The effect of MVP in macrophages on tumorigenesis and development was investigated by mouse primary liver cancer model and subcutaneous tumor transplantation model. The effect of MVP on the tumor microenvironment was investigated by multi-fluorescent immunohistochemical staining. The effect of MVP on CD8+ T cells was detected by cell co-culture, flow cytometry, qPCR, and ELISA.
The high expression of MVP in tumor-associated macrophages. The downregulation of the expression of MVP in tumor-associated macrophages compared with para-carcinoma tissues. MVP deficiency in macrophages promoted the proliferation and migration of tumor cells (P<0.05), promoted the development of tumor in vivo (P<0.05), formed an immunosuppressive microenvironment and weakened CD8+ T cell-mediated anti-tumor immunity (P<0.05).
MVP deficiency in macrophages can promote the occurrence and development of liver cancer by suppressing the function of CD8+ T cells.
Competing interests: The authors declare that they have no competing interests.
| [1] |
Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2024, 74(3): 229-263. doi: 10.3322/caac.21834
|
| [2] |
Forner A, Reig M, Bruix J. Hepatocellular carcinoma[J]. Lancet, 2018, 391(10127): 1301-1314. doi: 10.1016/S0140-6736(18)30010-2
|
| [3] |
Murciano-Goroff YR, Warner AB, Wolchok JD. The future of cancer immunotherapy: microenvironment-targeting combinations[J]. Cell Res, 2020, 30(6): 507-519. doi: 10.1038/s41422-020-0337-2
|
| [4] |
Vitale I, Manic G, Coussens LM, et al. Macrophages and Metabolism in the Tumor Microenvironment[J]. Cell Metab, 2019, 30(1): 36-50. doi: 10.1016/j.cmet.2019.06.001
|
| [5] |
Mantovani A, Sica A, Sozzani S, et al. The chemokine system in diverse forms of macrophage activation and polarization[J]. Trends Immunol, 2004, 25(12): 677-686. doi: 10.1016/j.it.2004.09.015
|
| [6] |
Cassetta L, Pollard JW. Targeting macrophages: therapeutic approaches in cancer[J]. Nat Rev Drug Discov, 2018, 17(12): 887-904. doi: 10.1038/nrd.2018.169
|
| [7] |
Berger W, Steiner E, Grusch M, et al. Vaults and the major vault protein: novel roles in signal pathway regulation and immunity[J]. Cell Mol Life Sci, 2009, 66(1): 43-61. doi: 10.1007/s00018-008-8364-z
|
| [8] |
Liu S, Hao Q, Peng N, et al. Major vault protein: a virus-induced host factor against viral replication through the induction of type-I interferon[J]. Hepatology, 2012, 56(1): 57-66. doi: 10.1002/hep.25642
|
| [9] |
Teng Y, Ren Y, Hu X, et al. MVP-mediated exosomal sorting of miR-193a promotes colon cancer progression[J]. Nat Commun, 2017, 8: 14448. doi: 10.1038/ncomms14448
|
| [10] |
Farhood B, Najafi M, Mortezaee K. CD8(+) cytotoxic T lymphocytes in cancer immunotherapy: A review[J]. J Cell Physiol, 2019, 234(6): 8509-8521. doi: 10.1002/jcp.27782
|
| [11] |
Jin HT, Anderson AC, Tan WG, et al. Cooperation of Tim-3 and PD-1 in CD8 T-cell exhaustion during chronic viral infection[J]. Proc Natl Acad Sci U S A, 2010, 107(33): 14733-14738. doi: 10.1073/pnas.1009731107
|
| [12] |
Dangaj D, Bruand M, Grimm AJ, et al. Cooperation between Constitutive and Inducible Chemokines Enables T Cell Engraftment and Immune Attack in Solid Tumors [J]. Cancer Cell, 2019, 35(6): 885-900. e10.
|
| [13] |
Bagheri H, Pourhanifeh MH, Derakhshan M, et al. CXCL-10: a new candidate for melanoma therapy?[J]. Cell Oncol (Dordr), 2020, 43(3): 353-365.
|
| [14] |
Hannesdóttir L, Tymoszuk P, Parajuli N, et al. Lapatinib and doxorubicin enhance the Stat1-dependent antitumor immune response[J]. Eur J Immunol, 2013, 43(10): 2718-2129. doi: 10.1002/eji.201242505
|
| [15] |
Amit I, Winter DR, Jung S. The role of the local environment and epigenetics in shaping macrophage identity and their effect on tissue homeostasis[J]. Nat Immunol, 2016, 17(1): 18-25. doi: 10.1038/ni.3325
|
| [16] |
Zhou L, Zhao T, Zhang R, et al. New insights into the role of macrophages in cancer immunotherapy[J]. Front Immunol, 2024, 15: 1381225. doi: 10.3389/fimmu.2024.1381225
|
| [17] |
Sun R, Lei C, Xu Z, et al. Neutral ceramidase regulates breast cancer progression by metabolic programming of TREM2-associated macrophages[J]. Nat Commun, 2024, 15(1): 966. doi: 10.1038/s41467-024-45084-7
|
| [18] |
Allavena P, Sica A, Solinas G, et al. The inflammatory micro-environment in tumor progression: the role of tumor-associated macrophages[J]. Crit Rev Oncol Hematol, 2008, 66(1): 1-9. doi: 10.1016/j.critrevonc.2007.07.004
|
| [19] |
Toledo B, Zhu Chen L, Paniagua-Sancho M, et al. Deciphering the performance of macrophages in tumour microenvironment: a call for precision immunotherapy[J]. J Hematol Oncol, 2024, 17(1): 44. doi: 10.1186/s13045-024-01559-0
|
| [20] |
Wherry EJ, Kurachi M. Molecular and cellular insights into T cell exhaustion[J]. Nat Rev Immunol, 2015, 15(8): 486-499. doi: 10.1038/nri3862
|
| [21] |
Hoch T, Schulz D, Eling N, et al. Multiplexed imaging mass cytometry of the chemokine milieus in melanoma characterizes features of the response to immunotherapy[J]. Sci Immunol, 2022, 7(70): eabk1692. doi: 10.1126/sciimmunol.abk1692
|
| [22] |
Tolomeo M, Cavalli A, Cascio A. STAT1 and Its Crucial Role in the Control of Viral Infections[J]. Int J Mol Sci, 2022, 23(8): 4095. doi: 10.3390/ijms23084095
|
| [23] |
Tokunaga R, Zhang W, Naseem M, et al. CXCL9, CXCL10, CXCL11/CXCR3 axis for immune activation - A target for novel cancer therapy[J]. Cancer Treat Rev, 2018, 63: 40-47. doi: 10.1016/j.ctrv.2017.11.007
|
| [24] |
Gardner A, de Mingo Pulido Á, Hänggi K, et al. TIM-3 blockade enhances IL-12-dependent antitumor immunity by promoting CD8+ T cell and XCR1+ dendritic cell spatial co-localization[J]. J Immunother Cancer, 2022, 10(1): e003571. doi: 10.1136/jitc-2021-003571
|
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