Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
권호 표지
DOI QR코드

DOI QR Code

Immunoregulatory Function of HLA-G in Gastric Cancer

  • Tuncel, Tolga (Department of Medical Oncology, Gata Haydarpasa Training Hospital) ;
  • Karagoz, Bulent (Department of Medical Oncology, Gata Haydarpasa Training Hospital) ;
  • Haholu, Aptullah (Department of Pathology, Gata Haydarpasa Training Hospital) ;
  • Ozgun, Alpaslan (Department of Medical Oncology, Gata Haydarpasa Training Hospital) ;
  • Emirzeoglu, Levent (Department of Medical Oncology, Gata Haydarpasa Training Hospital) ;
  • Bilgi, Oguz (Department of Medical Oncology, Gata Haydarpasa Training Hospital) ;
  • Kandemir, Emin Gokhan (Department of Medical Oncology, Gata Haydarpasa Training Hospital)
  • Published : 2013.12.31
Download PDF
⟨ Previous Next ⟩

Abstract

Background: Human leukocyte antigen (HLA)-G-positive gastric cancers are associated with poor survival, but links with tumor escape mechanisms remain to be determined. Materials and Methods: We used immunohistochemistry to investigate HLA-G expression, tumor infiltrating CD8+ T lymphocytes, and Treg cells in 52 gastric cancer patients. Results: There were 29 cancer-related deaths during the follow-up period. Kaplan-Meier analysis indicated that patients with HLA-G-positive (n=16) primary tumors had a significantly poorer prognosis than patients with HLA-G-negative tumors (n=36, p=0.008). The median survival time was 14 months and 47 months, respectively. Patients with high numbers of Tregs and low numbers of CD8+T lymphocytes in the primary tumor had a poorer prognosis than those with low numbers of Tregs and high numbers of CD8+T lymphocytes (p=0.034, p=0.043). Multivariate Cox proportional hazard regression analysis showed that HLA-G expression (hazard ratio: 2.662; 95% confidence interval: 1.242-5.723; p=0.012) and stage (hazard ratio: 2.012;95% confidence interval: 1.112-3.715; p=0.041) were independent unfavorable factors for patient survival. Conclusions: We found a significant positive correlation between HLA-G expression and the number of tumor infiltrating Tregs (p=0.01) and a negative correlation with the number of CD8+T lymphocytes (p=0.041). HLA-G may protect gastric cancer cells from cytolysis by inducing Foxp3+Treg lymphocytes and suppressing CD8+T lymphocytes.

Keywords

References

  1. Du L, Xiao X, Wang C, et al (2011). Human leukocyte antigen-G is closely associated with tumor immune escape in gastric cancer by increasing local regulatory T cells. Cancer Sci, 102, 1272-80. https://doi.org/10.1111/j.1349-7006.2011.01951.x
  2. Elliott RL, Jiang XP, Phillips JT, et al (2011). Human leukocyte antigen G expression in breast cancer: role in immunosuppression. Cancer Biother Radiopharm, 26, 135-7. https://doi.org/10.1089/cbr.2010.0831
  3. Guo Y, Lee CL, So KH, et al (2013). Soluble human leukocyte antigen-g5 activates extracellular signal-regulated protein kinase signaling and stimulates trophoblast invasion. Plos One, 8, 76023. https://doi.org/10.1371/journal.pone.0076023
  4. Ibrahim EC, Aractingi S, Allory Y, et al (2004). Analysis of HLA antigen expression in benign and malignant melanocytic lessions reveals that up regulation of HLA-G expression correlates with transformation, high inflammatory infiltration and HLA-A1 genotype. Int J Cancer, 108, 243-50. https://doi.org/10.1002/ijc.11456
  5. Ishigami S, Arigami T, Uenosono Y, et al (2012). Cancerous HLA class I expression and regulatory T cell infiltration in gastric cancer. Cancer Immunol Immunother, 61, 1663-9. https://doi.org/10.1007/s00262-012-1225-5
  6. Kotze D, Kruger TF, Lombard C, et al (2013). The effect of the biochemical marker soluble human leukocyte antigen G on pregnancy outcome in assisted reproductive technology-a multicenter study. Fertil Steril, 100, 1303-9. https://doi.org/10.1016/j.fertnstert.2013.07.1977
  7. Lin A, Zhang X, Zhou WJ, et al (2011). Human leukocyte antigen-G expression is associated with a poor prognosis in patients with esophageal squamous cell carcinoma. Int J Cancer, 129, 1382-90. https://doi.org/10.1002/ijc.25807
  8. Paul P, Rousas-Freiss N, Khalil-Daher I, et al (1998). HLA-G expression in melanoma, a way for tumor cells to escape from immunosurveillance. Proc Natl Acad Sci USA, 95, 4510-5. https://doi.org/10.1073/pnas.95.8.4510
  9. Paul P, Cabestre FA, Le Gal FA, et al (1999). Heterogeneity of HLA-G gene transcription and protein expression in malignant melanoma biopsies. Cancer res, 59, 1954-60.
  10. Peng LS, Zhuang Y, Shi Y, et al (2012). Increased tumorinfiltrating CD8+Foxp3+ T lymphocytes are associated with tumor progression in human gastric cancer. Cancer Immunol Immunother, 61, 2183-92. https://doi.org/10.1007/s00262-012-1277-6
  11. Yan WkH (2011). Human leukcyte antigen-G in cancer: Are they clinically relevant? Cancer Lett, 311, 123-30. https://doi.org/10.1016/j.canlet.2011.07.019
  12. Yie SM, Yang H, Ye SR, et al (2007). Expression of human leukocyte antigen G (HLA-G) correlates with poor prognosis in gastric carcinoma. Ann Surg Oncol, 14, 2721-9. https://doi.org/10.1245/s10434-007-9464-y
  13. Zeng XC, Zhang T, Huang DH, et al (2013). RNA interfering targeting human leukocyte antigen-G enhanced immune surveillance mediated by the natural killer cells on hepatocellular carcinoma. Ann Clin Lab Sci, 43, 135-44.

Cited by

  1. Pemetrexed is Mildly Active with Good Tolerability in Treating Patients with Gastric Cancer vol.15, pp.17, 2014, https://doi.org/10.7314/APJCP.2014.15.17.7137
  2. 14-bp Insertion/Deletion Polymorphism of the HLA-G gene in Breast Cancer among Women from North Western Iran vol.16, pp.14, 2015, https://doi.org/10.7314/APJCP.2015.16.14.6155
  3. TGF-β induces HLA-G expression through inhibiting miR-152 in gastric cancer cells vol.22, pp.1, 2015, https://doi.org/10.1186/s12929-015-0177-4
  4. 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 vol.37, pp.8, 2016, https://doi.org/10.1007/s13277-016-5002-5
  5. Long non-coding RNA HOTAIR modulates HLA-G expression by absorbing miR-148a in human cervical cancer vol.49, pp.3, 2016, https://doi.org/10.3892/ijo.2016.3589
  6. The Progress of T Cell Immunity Related to Prognosis in Gastric Cancer vol.2018, pp.2314-6141, 2018, https://doi.org/10.1155/2018/3201940
  7. HLA-G expression in gastric carcinoma: clinicopathological correlations and prognostic impact vol.473, pp.4, 2018, https://doi.org/10.1007/s00428-018-2379-0
  8. Heterogeneity of HLA-G Expression in Cancers: Facing the Challenges vol.9, pp.1664-3224, 2018, https://doi.org/10.3389/fimmu.2018.02164
  9. Prognostic role of tumor-infiltrating lymphocytes in gastric cancer vol.97, pp.32, 2018, https://doi.org/10.1097/MD.0000000000011769
  10. HLA-G Gene Polymorphism in Egyptian Patients with Non-Hodgkin Lymphoma and its Clinical Outcome vol.47, pp.3, 2018, https://doi.org/10.1080/08820139.2018.1430826