CCR3, CCR4, CCR5, and CXCR3 expression in peripheral blood CD4+ lymphocytes in gastric cancer patients

Authors
Alireza Andalib
Hassan Doulabi
Mohammad Reza Maracy
Abbas Rezaei
Seyed Javad Hasheminia
Department of Immunology, Isfahan Medical School, Isfahan University of Medical Sciences, Isfahan, Iran
Abstract
Background: CD4+(TH1, and TH2) cell groups in the point of view of chemokine receptor expression were considered in blood of stomach cancer patients.
Materials and Methods: The percentage of blood CD4+ T cells expressing chemokine receptors (before and after gastrectomy) was determined by flow cytometry (Becton Dickinson, USA) using the following chemokine receptor antibodies: anti-CCR5, anti-CXCR3, anti-CCR3 and anti-CCR4.
Results: The means of CD4 + CCR5 + expressing cells was 1.23% ± 0.90, 0.83% ± 0.34 and 1.34% ± 0.74 in control, pre- and post-operation groups, respectively. CD4 + CXCR3 + expressing cells were 19.09% ± 8.4, 16.95% ± 5.71 and 25.08% ± 9.31, respectively. Similar pattern was seen for CD4 + CCR3 + and CD4 + CCR4 + expressing cells. Pearson correlation analysis shows no relationship between CCR3 and CCR4 expressions on TCD4 cells (r = 0.211, P = 0.126). The complex expression TH1 (CD4 + CXCR3 + CCR5 + ) receptors determined 1.14% ± 0.54 for control group, 0.86% ± 0.49 for pre-T and 1.57% ± 0.67 for post-T group. Moreover, the TH2 (CD4 + CCR3 + CCR4 + ) expression was 1.60% ± 1.05 for control group, 1.57% ± 0.83 for pre-T and 1.27% ± 0.66 for post-treatment group. Pearson correlation analysis shows that only the CCR3 and CCR5 expression was statistically correlated (r = 0.321, P = 0.018).
Conclusion: Due to low expression of CCR5 in TH1 and CCR3 in TH2 cells, it seems that utility of these is extremely limited for clinical evaluation, but not scientific purpose. Moreover, considering the CXCR3 for TH1 cells and CCR4 expression for TH2 cells, due to considerable expression, may be practical.

Keywords

 
1. Shurin MR, Shurin GV, Lokshin A, Yurkovetsky ZR, Gutkin DW, Chatta G, et al. Intratumoral cytokines/chemokines/growth factors and tumor infiltrating dendritic cells: friends or enemies? Cancer Metastasis Rev 2006;25:333-56.  Back to cited text no. 1
[PUBMED]    
2. Viola A, Contento RL, Molon B. T cells and their partners: The chemokine dating agency. Trends Immunol 2006;27:421-7.  Back to cited text no. 2
[PUBMED]    
3. Sallusto F, Lanzavecchia A, Mackay CR. Chemokines and chemokine receptors in T-cell priming and Th1/Th2-mediated responses. Immunol Today 1998;19:568-74.  Back to cited text no. 3
[PUBMED]    
4. Tabata T, Hazama S, Yoshino S, Oka M. Th2 subset dominance among peripheral blood T lymphocytes in patients with digestive cancers. Am J Surg 1999;177:203-8.  Back to cited text no. 4
[PUBMED]    
5. Reinartz S, Boerner H, Koehler S, Von RA, Schlebusch H, Wagner U. Evaluation of immunological responses in patients with ovarian cancer treated with the anti-idiotype vaccine ACA125 by determination of intracellular cytokines--a preliminary report. Hybridoma 1999;18:41-5.  Back to cited text no. 5
    
6. Luo Y, Chen X, Downs TM, DeWolf WC, O'Donnell MA. IFN-alpha 2B enhances Th1 cytokine responses in bladder cancer patients receiving Mycobacterium bovis bacillus Calmette-Guerin immunotherapy. J Immunol 1999;162:2399-405.  Back to cited text no. 6
[PUBMED]    
7. Hrouda D, Baban B, Dunsmuir WD, Kirby RS, Dalgleish AG. Immunotherapy of advanced prostate cancer: A phase I/II trial using Mycobacterium vaccae (SRL172). Br J Urol 1998;82:568-73.  Back to cited text no. 7
[PUBMED]    
8. Shurin MR, Lu L, Kalinski P, Stewart-Akers AM, Lotze MT. Th1/Th2 balance in cancer, transplantation and pregnancy. Springer Semin Immunopathol 1999;21:339-59.  Back to cited text no. 8
[PUBMED]    
9. De ST, Van MM, De BG, Urbain J, Leo O, Moser M. Effect of interleukin-10 on dendritic cell maturation and function. Eur J Immunol 1997;27:1229-35.  Back to cited text no. 9
    
10. Yang P, Qiu G, Wang S, Su Z, Chen J, Wang S, et al. The mutations of Th1 cell-specific T-box transcription factor may be associated with a predominant Th2 phenotype in gastric cancers. Int J Immunogenet 2010;37:111-5.  Back to cited text no. 10
[PUBMED]    
11. Mosmann TR, Sad S. The expanding universe of T-cell subsets: Th1, Th2 and more. Immunol Today 1996;17:138-46.  Back to cited text no. 11
[PUBMED]    
12. Raman D, Baugher PJ, Thu YM, Richmond A. Role of chemokines in tumor growth. Cancer Lett 2007;256:137-65.  Back to cited text no. 12
[PUBMED]    
13. Allen SJ, Crown SE, Handel TM. Chemokine: Receptor structure, interactions,and antagonism. Annu Rev Immunol 2007;25:787-820.  Back to cited text no. 13
[PUBMED]    
14. Ruffini PA, Morandi P, Cabioglu N, Altundag K, Cristofanilli M. Manipulating the chemokine-chemokine receptor network to treat cancer. Cancer 2007;109:2392-404.  Back to cited text no. 14
[PUBMED]    
15. Sugasawa H, Ichikura T, Kinoshita M, Ono S, Majima T, Tsujimoto H, et al. Gastric cancer cells exploit CD4+ cell-derived CCL5 for their growth and prevention of CD8+ cell-involved tumor elimination. Int J Cancer 2008;122:2535-41.  Back to cited text no. 15
[PUBMED]    
16. Janeway CA, Travers P, Walport M, Shlomchik MJ. Immunobiology. 7 th ed. Philadelphia: Churchill Livingstone; 2007.  Back to cited text no. 16
    
17. Nishimura T, Iwakabe K, Sekimoto M, Ohmi Y, Yahata T, Nakui M, et al. Distinct role of antigen-specific T helper type 1 (Th1) and Th2 cells in tumor eradication in vivo. J Exp Med 1999;190:617-27.  Back to cited text no. 17
[PUBMED]    
18. Fujii K, Sonoda K, Izumi K, Shiraishi N, Adachi Y, Kitano S. T lymphocyte subsets and Th1/Th2 balance after laparoscopy-assisted distal gastrectomy. Surg Endosc 2003;17:1440-4.  Back to cited text no. 18
[PUBMED]    
19. Liu XL, Gao J, Han CZ, Qiao LJ. [Pre- and post-chemotherapy expressions of Th1 and Th2 type cytokines and their clinical significance in gastric cancer patients]. Zhonghua Zhong Liu Za Zhi 2008;30:844-7.  Back to cited text no. 19
[PUBMED]    
20. M.G. Macey (Ed.),. Flow Cytometry: Principles and Applications. Humana Press, Totowa,. NJ. 15. 2007.  Back to cited text no. 20
    
21. Cavallo F, Curcio C, Forni G. Immunotherapy and immunoprevention of cancer: Where do we stand? Expert Opin Biol Ther 2005;5:717-26.  Back to cited text no. 21
[PUBMED]    
22. Negus RP, Stamp GW, Hadley J, Balkwill FR. Quantitative assessment of the leukocyte infiltrate in ovarian cancer and its relationship to the expression of C-C chemokines. Am J Pathol 1997;150:1723-34.  Back to cited text no. 22
[PUBMED]    
23. Zhu J, Paul WE. CD4 T cells: Fates, functions, and faults. Blood 2008;112:1557-69.  Back to cited text no. 23
[PUBMED]    
24. Paul WE. Fundamental Immunology. USA: Lippincott williams and wilkins; 2008.  Back to cited text no. 24
    
25. Asano N, Suzuki R, Ohshima K, Kagami Y, Ishida F, Yoshino T, et al. Linkage of expression of chemokine receptors (CXCR3 and CCR4) and cytotoxic molecules in peripheral T cell lymphoma, not otherwise specified and ALK-negative anaplastic large cell lymphoma. Int J Hematol 2010;91:426-35.  Back to cited text no. 25
[PUBMED]    
26. Yoon SH, Yun SO, Park JY, Won HY, Kim EK, Sohn HJ, et al. Selective addition of CXCR3(+) CCR4(-) CD4(+) Th1 cells enhances generation of cytotoxic T cells by dendritic cells in vitro. Exp Mol Med 2009;41:161-70.  Back to cited text no. 26
[PUBMED]    
27. Ishikawa M, Nishioka M, Hanaki N, Miyauchi T, Kashiwagi Y, Ioki H, et al. Perioperative immune responses in cancer patients undergoing digestive surgeries. World J Surg Oncol 2009;7:7.  Back to cited text no. 27
[PUBMED]    
28. Pellegrini P, Berghella AM, Del BT, Cicia S, Adorno D, Casciani CU. Disregulation in TH1 and TH2 subsets of CD4+ T cells in peripheral blood of colorectal cancer patients and involvement in cancer establishment and progression. Cancer Immunol Immunother 1996;42:1-8.  Back to cited text no. 28
    
29. Pellegrini P, Contasta I, Berghella AM, Del BT, Casciani CU, Adorno D. The TH1 and TH2 cytokine network in healthy subjects: suggestions for experimental studies to create prognostic and diagnostic indices for biotherapeutic treatments. Cancer Biother Radiopharm 2000;15:267-78.  Back to cited text no. 29
    
30. Berghella AM, Pellegrini P, Del BT, Marini M, Tomei E, Adorno D, et al. The significance of an increase in soluble interleukin-2 receptor level in colorectal cancer and its biological regulating role in the physiological switching of the immune response cytokine network from TH1 to TH2 and back. Cancer Immunol Immunother 1998;45:241-9.  Back to cited text no. 30
    
Advanced Biomedical Research
Volume 2013, March
March 2013
Pages 1-8