Open Access

Immunoglobulin‑like transcript 4 and human leukocyte antigen‑G interaction promotes the progression of human colorectal cancer

  • Authors:
    • Zhaoyang Cai
    • Lu Wang
    • Yali Han
    • Wenwen Gao
    • Xiaojuan Wei
    • Rumei Gong
    • Mingliang Zhu
    • Yuping Sun
    • Shuwen Yu
  • View Affiliations

  • Published online on: March 22, 2019     https://doi.org/10.3892/ijo.2019.4761
  • Pages: 1943-1954
  • Copyright: © Cai et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Immunoglobulin‑like transcript (ILT) 4, a negative regulator of immune response in allograft rejection, autoimmunity and infectious diseases, has recently been determined to serve important roles in tumor development. In the present study, the co‑expression of ILT4 and human leukocyte antigen‑G (HLA‑G) in tissues of human primary colorectal cancer (CRC) was revealed, and its association with older age, advanced stage, regional lymph node involvement and poor overall survival time was identified. In CRC cell lines, ILT4 and HLA‑G co‑expression and their autocrine regulation was demonstrated. ILT4 interference affected HLA‑G expression and regulated the cell proliferation, invasion and migration of CRC. HLA‑G fusion protein treatment also increased ILT4 expression in a dose‑dependent manner, thereby activating protein kinase B (AKT) and extracellular signal‑regulated kinase (ERK) signaling, and facilitating the proliferation, migration and invasion of CRC cells. Additionally, the AKT and ERK activation, and CRC cell malignant characteristics induced by HLA‑G may be suppressed by blocking ILT4. The present results indicated that the interaction of ILT4 and its ligand HLA‑G promotes CRC progression through AKT and ERK signal activation, providing a novel strategy of blocking ILT4/HLA‑G for the treatment of CRC.

References

1 

Liang R, Lin Y, Yuan CL, Liu ZH, Li YQ, Luo XL, Ye JZ and Ye HH: High expression of estrogen related receptor α is signifi cantly associated with poor prognosis in patients with colorectal cancer. Oncol Lett. 15:5933–5939. 2018.PubMed/NCBI

2 

Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D and Bray F: Cancer incidence and mortality worldwide: Sources methods and major patterns in GLOBOCAN 2012. Int J Cancer. 136:E359–E386. 2015. View Article : Google Scholar

3 

Petera J, Dušek L, Sirák I, Soumarova R and Jarkovsky J: Cancer in the elderly in the Czech Republic. Eur J Cancer Care (Engl). 24:163–178. 2015. View Article : Google Scholar

4 

Pitule P, Vycital O, Bruha J, Novak P, Hosek P, Treska V, Hlavata I, Soucek P, Kralickova M and Liska V: Differential expression and prognostic role of selected genes in colorectal cancer patients. Anticancer Res. 33:4855–4865. 2013.PubMed/NCBI

5 

Colonna M, Nakajima H and Cella M: A family of inhibitory and activating Ig like receptors that modulate function of lymphoid and myeloid cells. Semin Immunol. 12:121–127. 2000. View Article : Google Scholar : PubMed/NCBI

6 

Borges L and Cosman D: LIRs/ILTs/MIRs, inhibitory and stimulatory Ig superfamily receptors expressed in myeloid and lymphoid cells. Cytokine Growth Factor Rev. 11:209–217. 2000. View Article : Google Scholar : PubMed/NCBI

7 

Shiroishi M, Tsumoto K, Amano K, Shirakihara Y, Colonna M, Braud VM, Allan DS, Makadzange A, Rowland Jones S, Willcox B, et al: Human inhibitory receptors Ig like transcript 2 (ILT2) and ILT4 compete with CD8 for MHC class I binding and bind preferentially to HLA-G. Proc Natl Acad Sci USA. 100:8856–8861. 2003. View Article : Google Scholar

8 

Nakajima H, Asai A, Okada A, Ping L, Hamajima F, Sata T and Isobe K: Transcriptional regulation of ILT family receptors. J Immunol. 171:6611–6620. 2003. View Article : Google Scholar : PubMed/NCBI

9 

Sun Y, Liu J, Gao P, Wang Y and Liu C: Expression of Ig like transcript 4 inhibitory receptor in human non small cell lung cancer. Chest. 134:783–788. 2008. View Article : Google Scholar : PubMed/NCBI

10 

Liu J, Wang L, Gao W, Li L, Cui X, Yang H, Lin W, Dang Q, Zhang N and Sun Y: Inhibitory receptor immunoglobulin like transcript 4 was highly expressed in primary ductal and lobular breast cancer and significantly correlated with IL 10. Diagn Pathol. 9:852014. View Article : Google Scholar

11 

Zhang Y, Zhao J, Qiu L, Zhang P, Li J, Yang D, Wei X, Han Y, Nie S and Sun Y: Co expression of ILT4/HLA-G in human non small cell lung cancer correlates with poor prognosis and ILT4 HLA-G interaction activates ERK signaling. Tumour Biol. 37:11187–11198. 2016. View Article : Google Scholar : PubMed/NCBI

12 

Djurisic S and Hviid TV: HLA Class Ib Molecules and Immune Cells in Pregnancy and Preeclampsia. Front Immunol. 5:6522014. View Article : Google Scholar

13 

LeMaoult J, Zafaranloo K, Le Danff C and Carosella ED: HLA-G up regulates ILT2, ILT3, ILT4, and KIR2DL4 in antigen presenting cells, NK cells, and T cells. FASEB J. 19:662–664. 2005. View Article : Google Scholar : PubMed/NCBI

14 

Köstlin N, Ostermeir AL, Spring B, Schwarz J, Marmé A, Walter CB, Poets CF and Gille C: HLA-G promotes myeloid derived suppressor cell accumulation and suppressive activity during human pregnancy through engagement of the receptor ILT4. Eur J Immunol. 47:374–384. 2017. View Article : Google Scholar

15 

Rouas Freiss N, Moreau P, LeMaoult J and Carosella ED: The dual role of HLA-G in cancer. J Immunol Res. 2014:3597482014. View Article : Google Scholar : PubMed/NCBI

16 

Rouas Freiss N, LeMaoult J, Verine J, Tronik Le, Roux D, Culine S, Hennequin C, Desgrandchamps F and Carosella ED: Intratumor heterogeneity of immune checkpoints in primary renal cell cancer: Focus on HLA-G/ILT2/ILT4. OncoImmunology. 6:e13420232017. View Article : Google Scholar : PubMed/NCBI

17 

Özgül Özdemir RB, Özdemir AT, Oltulu F, Kurt K, Yiğittürk G and Kırmaz C: A comparison of cancer stem cell markers and nonclassical major histocompatibility complex antigens in colorectal tumor and noncancerous tissues. Ann Diagn Pathol. 25:60–63. 2016. View Article : Google Scholar : PubMed/NCBI

18 

Alaoui L, Palomino G, Zurawski S, Zurawski G, Coindre S, Dereuddre Bosquet N, Lecuroux C, Goujard C, Vaslin B, Bourgeois C, et al: Early SIV and HIV infection promotes the LILRB2/MHC I inhibitory axis in cDCs. Cell Mol Life Sci. 75:1871–1887. 2018. View Article : Google Scholar

19 

Nowak I, Wilczyńska K, Wilczyński JR, Malinowski A, Radwan P, Radwan M and Kuśnierczyk P: KIR, LILRB and their Ligands’ Genes as Potential Biomarkers in Recurrent Implantation Failure. Arch Immunol Ther Exp (Warsz). 65:391–399. 2017. View Article : Google Scholar

20 

Guerra de Blas PC, Villaseñor Talavera YS, Cruz González DJ, Ba randa L, Doníz Padilla L, Abud Mendoza C, González Amaro R and Monsiváis Urenda AE: Analysis of the Expression and Function of Immunoglobulin Like Transcript 4 (ILT4, LILRB2) in Dendritic Cells from Patients with Systemic Lupus Erythematosus. J Immunol Res. 2016:41630942016. View Article : Google Scholar

21 

Edge SB and Compton CC: The American Joint Committee on Cancer: The 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 17:1471–1474. 2010. View Article : Google Scholar : PubMed/NCBI

22 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real time quantitative PCR and the 2(Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar

23 

Gao A, Sun Y and Peng G: ILT4 functions as a potential checkpoint molecule for tumor immunotherapy. Biochim Biophys Acta Rev Cancer. 1869:278–285. 2018. View Article : Google Scholar : PubMed/NCBI

24 

Castellaneta A, Mazariegos GV, Nayyar N, Zeevi A and Thomson AW: HLA-G level on monocytoid dendritic cells correlates with regulatory T cell Foxp3 expression in liver transplant tolerance. Transplantation. 91:1132–1140. 2011. View Article : Google Scholar : PubMed/NCBI

25 

Liang S, Ristich V, Arase H, Dausset J, Carosella ED and Horuzsko A: Modulation of dendritic cell differentiation by HLA-G and ILT4 requires the IL 6 STAT3 signaling pathway. Proc Natl Acad Sci USA. 105:8357–8362. 2008. View Article : Google Scholar

26 

Ristich V, Zhang W, Liang S and Horuzsko A: Mechanisms of prolongation of allograft survival by HLA-G/ILT4 modified dendritic cells. Hum Immunol. 68:264–271. 2007. View Article : Google Scholar : PubMed/NCBI

27 

Carosella ED, Rouas Freiss N, Tronik Le, Roux D, Moreau P and LeMaoult J: HLA-G: An Immune Checkpoint Molecule. Adv Immunol. 127:33–144. 2015. View Article : Google Scholar : PubMed/NCBI

28 

Apps R, Gardner L and Moffett A: A critical look at HLA-G. Trends Immunol. 29:313–321. 2008. View Article : Google Scholar : PubMed/NCBI

29 

Zeestraten EC, Reimers MS, Saadatmand S, Goossens Beumer IJ, Dekker JW, Liefers GJ, van den Elsen PJ, van de Velde CJ and Kuppen PJ: Combined analysis of HLA class I, HLA E and HLA-G predicts prognosis in colon cancer patients. Br J Cancer. 110:459–468. 2014. View Article : Google Scholar

30 

Guo ZY, Lv YG, Wang L, Shi SJ, Yang F, Zheng GX, Wen WH and Yang AG: Predictive value of HLA-G and HLA E in the prognosis of colorectal cancer patients. Cell Immunol. 293:10–16. 2015. View Article : Google Scholar

31 

Reimers MS, Engels CC, Putter H, Morreau H, Liefers GJ, van de Velde CJ and Kuppen PJ: Prognostic value of HLA class I, HLA E, HLA-G and Tregs in rectal cancer: A retrospective cohort study. BMC Cancer. 14:4862014. View Article : Google Scholar

Related Articles

Journal Cover

June 2019
Volume 54 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Cai, Z., Wang, L., Han, Y., Gao, W., Wei, X., Gong, R. ... Yu, S. (2019). Immunoglobulin‑like transcript 4 and human leukocyte antigen‑G interaction promotes the progression of human colorectal cancer. International Journal of Oncology, 54, 1943-1954. https://doi.org/10.3892/ijo.2019.4761
MLA
Cai, Z., Wang, L., Han, Y., Gao, W., Wei, X., Gong, R., Zhu, M., Sun, Y., Yu, S."Immunoglobulin‑like transcript 4 and human leukocyte antigen‑G interaction promotes the progression of human colorectal cancer". International Journal of Oncology 54.6 (2019): 1943-1954.
Chicago
Cai, Z., Wang, L., Han, Y., Gao, W., Wei, X., Gong, R., Zhu, M., Sun, Y., Yu, S."Immunoglobulin‑like transcript 4 and human leukocyte antigen‑G interaction promotes the progression of human colorectal cancer". International Journal of Oncology 54, no. 6 (2019): 1943-1954. https://doi.org/10.3892/ijo.2019.4761