Peripheral blood CD4+CRTH2+ cells in advanced stage non small cell lung cancer

• Autorzy: Bülent Karagöz , Oğuz Bilgi , Emin Kandemir , Alev Erikçi , Özkan Sayan , Alpaslan Özgün , Bahattin Yılmaz , Orhan Türken , Ahmet Alacacıoğlu , Ahmet Öztürk
• Języki publikacji: EN

Abstrakty

EN

To investigate CD4+CRTH2+ cells in peripheral blood in advanced stage non small cell lung cancer (NSCLC) patients. Forty-six patients with advanced stage NSCLC, who are chemotherapy or radiotherapy naïve, and 17 healthy volunteers, were enrolled in this study. The study was performed using flow cytometry and a complete blood cell counter analyser. CD4+ T cell percentage, CD4/CD8 ratio, CRTH2+CD4+ cell percentages, counts, and mean fluorescein intensity (MFI) and hematological parameters were evaluated in both groups. A survival analysis was performed to compare the patients with high CD4+CRTH2+ cell percentage and those with low CD4+CRTH2+ percentage. CD4+ T cell percentage in total lymphocytes and the CD4/CD8 ratio were lower in the patient group than in the control group. The absolute CD8 T cell count was higher in the patient group than in the control group, whereas the total T cells was not different. The CRTH2+ cell percentage in CD4+ T cells (7.96% ± 6.21% vs 3.37% ± 3.55%; respectively; p: 0,001) and the absolute count of CRTH2+CD4+ cells ( 97 mm-3 ± 109 mm-3 vs 37 mm-3 ± 38 mm-3, respectively; p: 0,033) in the patient group were higher than in the control group, but CRTH2-PE MFI values were not different between groups. Cox regression analysis did not show that CRTH2+CD4+ cell count or percentage is an independent prognostic factor. The study found that CRTH2 expression of CD4+ T cells and CRTH2+CD4+ cell number are higher in the peripheral blood of NSCLC patients than in that of healthy subjects. Further studies that explore the biological significance of high CD4+CRTH2+ cells in lung cancer patients, should be pursued.

Słowa kluczowe

EN

Lung cancer; CRTH2; Th2 cells; Immunity; Survival

• Czasopismo: Open Medicine
• Rocznik: 2010
• Tom: 5
• Numer: 4
• Strony: 431-436

Daty

wydano

2010-08-01

online

2010-05-30

Twórcy

autor

Bülent Karagöz

• GATA Haydarpasa Training Hospital Department of Medical Oncology, Haydarpasa, 34667, Istanbul, Turkey,

autor

Oğuz Bilgi

• GATA Haydarpasa Training Hospital Department of Medical Oncology, Haydarpasa, 34667, Istanbul, Turkey

autor

Emin Kandemir

• GATA Haydarpasa Training Hospital Department of Medical Oncology, Haydarpasa, 34667, Istanbul, Turkey

autor

Alev Erikçi

• GATA Haydarpasa Training Hospital Department of Hematology Haydarpasa, 34667, Istanbul, Turkey

autor

Özkan Sayan

• GATA Haydarpasa Training Hospital Department of Hematology Haydarpasa, 34667, Istanbul, Turkey

autor

Alpaslan Özgün

• GATA Haydarpasa Training Hospital Department of Medical Oncology, Haydarpasa, 34667, Istanbul, Turkey

autor

Bahattin Yılmaz

• GATA Haydarpasa Training Hospital Department of Medical Oncology, Haydarpasa, 34667, Istanbul, Turkey

autor

Orhan Türken

• GATA Haydarpasa Training Hospital Department of Medical Oncology, Haydarpasa, 34667, Istanbul, Turkey

autor

Ahmet Alacacıoğlu

• GATA Haydarpasa Training Hospital Department of Medical Oncology, Haydarpasa, 34667, Istanbul, Turkey

autor

Ahmet Öztürk

• GATA Haydarpasa Training Hospital Department of Hematology Haydarpasa, 34667, Istanbul, Turkey

Bibliografia

• [1] Hata AN, Breyer RM. Pharmacology and signaling of prostaglandin receptors: multiple roles in inflammation and immune modulation. Pharmacol Ther 2004;103:147–166 http://dx.doi.org/10.1016/j.pharmthera.2004.06.003[Crossref]
• [2] Nagata K, Hirai H. The second PGD(2) receptor CRTH2: structure, properties, and functions in leukocytes. Prostaglandins Leukot Essent Fatty Acids 2003;69:169–177 http://dx.doi.org/10.1016/S0952-3278(03)00078-4[Crossref]
• [3] Tanaka K, Hirai H, Takano S, Nakamura M, Nagata K. Effects of prostaglandin D2 on helper T cell functions. Biochem Biophys Res Commun 2004;316:1009–1014 http://dx.doi.org/10.1016/j.bbrc.2004.02.151[Crossref]
• [4] Nagata K, Hirai H, Tanaka K, Ogawa K, Aso T, Sugamura K et al. CRTH2, an orphan receptor of T-helper-2-cells, is expressed on basophils and eosinophils and responds to mast cell-derived factor(s). FEBS Lett. 1999;459:195–199 http://dx.doi.org/10.1016/S0014-5793(99)01251-X[Crossref]
• [5] Hirai H, Tanaka K, Yoshie O, Ogawa K, Kenmotsu K, Takamori Y et al. Prostaglandin D2 selectively induces chemotaxis in T helper type 2 cells, eosinophils, and basophils via even transmembrane receptor CRTH2. J Exp Med 2001;193:255–261 http://dx.doi.org/10.1084/jem.193.2.255[Crossref]
• [6] Ellyard JI, Simson L, Parish CR. Th 2-mediated antitumour immunity: friend or foe? Tissue Antigens 2007;70:1–11 http://dx.doi.org/10.1111/j.1399-0039.2007.00869.x[WoS][Crossref]
• [7] Takanami I, Takeuchi K, Gika M. Immunohistochemical detection of eosinophilic infiltration in pulmonary adenocarcinoma. Anticancer Res 2002;22:2391–2396
• [8] Cosmi L, Annunziato F, Galli MIG, Maggi RME, Nagata K, Romagnani S. CRTH 2 is the most reliable marker for the detection of circulating human type 2 Th and type 2 T cytotoxic cells in health and disease. 2 Th and type 2 T cytotoxic cells in health and disease. Eur J Immunol 2000;30:2972–2979 http://dx.doi.org/10.1002/1521-4141(200010)30:10<2972::AID-IMMU2972>3.0.CO;2-#[Crossref]
• [9] Wang YH, Ito T, Wang YH, Homey B, Watanabe N, Martin R et al. Maintenance and polarization of human TH2 central memory T cells by thymic stromal lymphopoietin activated dendritic cells. Immunity 2006;24:827–838 http://dx.doi.org/10.1016/j.immuni.2006.03.019[Crossref]
• [10] Kim N, Luster AD. Regulation of immune cells by eicosanoid receptors. Scientific World Journal 2007;7:1307–1328 [Crossref]
• [11] Aspord C, Pedroza-Gonzalez A, Gallegos M, Tindle S, Burton EC, Su D et al. Breast cancer instructs dendritic cells to prime interleukin 13-secreting CD4+ T cells that facilitate tumor development. J Exp Med 2007;204:1037–1047 http://dx.doi.org/10.1084/jem.20061120[WoS][Crossref]
• [12] Venet F, Lepape A, Debard AL, Bienvenu J, Bohe J, Monneret G. The Th2 response as monitored by CRTH2 or CCR3 expression is severely decreased during septic shock. Clin Immunol 2004;113:278–284 http://dx.doi.org/10.1016/j.clim.2004.07.005[Crossref]
• [13] Mattes J, Hulett M, Xie W, Hogan S, Rothenberg ME, Foster P et al. Immunotherapy of cytotoxic T cell-resistant tumors by T helper 2 cells: an eotaxin and STAT6-dependent process. J Exp Med 2003;197:387–393 http://dx.doi.org/10.1084/jem.20021683[Crossref]
• [14] Chu Y, Xia M, Lin Y, Li A, Wang Y, Liu R et al. Th2-dominated antitumor immunity induced by DNA immunization with the genes coding for a basal core peptide PDTRP and GM-CSF. Cancer Gene Ther 2006;13:510–519 http://dx.doi.org/10.1038/sj.cgt.7700913[Crossref]
• [15] Mautner J, Jaffee EM, Pardoll DM. Tumorspecific CD4+ T cells from a patient with renal cell carcinoma recognize diverse shared antigens. Int J Cancer 2005;115:752–759 http://dx.doi.org/10.1002/ijc.20927[Crossref]
• [16] Tepper RI, Coffman RL, Leder P. An eosinophildependent mechanism for the antitumor effect of interleukin-4. Science 1992;257:548–551 http://dx.doi.org/10.1126/science.1636093[Crossref]
• [17] Pericle F, Giovarelli M, Colombo MP, Ferrari G, Musiani P, Modesti A et al. An efficient Th2-type memory follows CD8+ lymphocyte-driven and eosinophil-mediated rejection of a spontaneous mouse mammary adenocarcinoma engineered to release IL-4. J Immunol 1994;153:5659–5673
• [18] Saleh M, Davis ID, Wilks AF. The paracrine role of tumour-derived mIL-4 on tumour associated endothelium. Int J Cancer 1997;72:664–672 http://dx.doi.org/10.1002/(SICI)1097-0215(19970807)72:4<664::AID-IJC19>3.0.CO;2-B[Crossref]
• [19] Schuler T, Kornig S, Blankenstein T. Tumor rejection by modulation of tumor stromal fibroblasts. J Exp Med 2003;198:1487–1493 http://dx.doi.org/10.1084/jem.20030849[Crossref]
• [20] Lebel-Binay S, Laguerre B, Quintin-Colonna F, Conjeaud H, Magazin M, Miloux B et al. Experimental gene therapy of cancer using tumor cells engineered to secrete interleukin-13. Eur J Immunol 1995;25:2340–2348 http://dx.doi.org/10.1002/eji.1830250833[Crossref]
• [21] Ma HL, Whitters MJ, Jacobson BA, Donaldson DD, Collins M, Dunussi-Joannopoulos K. Tumor cells secreting IL-13 but not IL-13Ralpha2 fusion protein have reduced tumorigenicity in vivo. Int Immunol 2004;16:1009–1017 http://dx.doi.org/10.1093/intimm/dxh105

Identyfikatory

DOI

10.2478/s11536-009-0047-0