Surface vs. intracellular CTLA-4 expression in lung cancer

Cytotoxic T-Lymphocyte Antigen 4 (CTLA- 4) is a molecule capable to down-regulate T cell activation thus suppress anticancer response.CTLA-4 is identified as surface ( s ) or intracellular ( in ) antigen. The physiologic regulation causes immediate endocytosis of surface molecule, the majority of CTLA-4 is localized in intracellular granules. The aim of the study was to compare of s and in CTLA-4 expression on T regulatory cells (CD4/CD25 high ) in the blood of lung cancer patients and healthy control subjects. Flow cytometry with the mixture of antibodies anti: CD4/CD25/CTLA-4 revealed CTLA-4 positive cells. For evaluation the in CTLA-4 expression we incubated the cells with Transcription Factor Buffer (BD). We analysed proportion of CD4/CTLA4, CD4/CD25/CTLA4 and CD4/CD25 high /CTLA-4 populations and we observed the most prominent alteration in the last cells. There was significantly higher proportion (23.4 vs.6.1, p<0.05) and expression (Median Fluorescence Intensity: 543 vs. 484,p<0.05) of in CTLA-4+ cells than s CTLA-4+. The reverse correlation of s CTLA-4+ with in CTLA-4+ cells was noticed. The s CTLA-4+ to in CTLA-4+- ratio was significantly higher in the blood of lung cancer patients when compared with healthy (27 vs.7.6, p<0.05).The median proportion of s CTLA-4+ cells differed significantly between cancer patients and healthy (6.7 vs.2.1, p<0.05), but the difference of in CTLA-4+ was opposite (21.1 vs.28, p<0.05). Concluding, we presume that the CTLA-4 cellular traffic in lung cancer is modified by microenvironment towards enhanced surface expression.