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

Abstract

<jats:title>Abstract</jats:title><jats:p>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.</jats:p>

The therapeutic potential of CRTH2/DP2 beyond allergy and asthma

“…Some of the pro-apoptotic properties of PGD2 and its metabolites such as 15-deoxy-PGJ 2 can be attributed to both PPARγ activation and a receptor-independent mechanism, such as modulation of intracellular redox potential in osteosarcoma cells [ 114 ], but a clear contribution of CRTH2-mediated effects is also given: CRTH2 activation can induce apoptosis via autocrine stimulation of both reactive oxygen species and TNF-α production in a MAPK pathway-dependent manner in cardiomyocytes [ 115 ], and via Erk1/2 and Akt signaling in human osteoclasts [ 77 ]. Although, these in-vitro data suggest anti-tumorigenic properties, the exact role of CRTH2 in cancer is still unclear: CRTH2 expression on circulating CD4 positive cells was elevated in the late stage of non-small cell lung cancer [ 116 ], and in an experimental model using Lewis lung carcinoma cells implanted on the back of mice, CRTH2 expression was detected in vascular cells and the growing tumor [ 117 ]. Furthermore, in 277 samples of human gastric cancer, 17% of cases showed cancer cells positive for CRTH2 [ 118 ] and polarized group 2 innate lymphoid cells (ILC2) with increased levels of CRTH2 were found in the peripheral blood of gastric cancer patients [ 119 ].…”