Flowcytometric immunophenotyping of peripheral-blood leukocytes in relation to immunopathology and cellular proliferation of pleural mesothelioma

Immunomodulation of malignant mesothelioma (MM) is variable considering host immune mechanisms. This study has investigated the immunophenotyping of peripheral-blood leukocytes of patients with mesothelioma in relation to different histopathologic types and proliferative potentiality. The study was achieved on 18 patients presented by massive effusion accompanying MM. Circulating CD4+ and CD8+ T cells were counted using two-colour flowcytometry. Pleural effusion cell block preparation and pleural biopsies were processed for immunohistochemical analysis of intratumoral CD8+ lymphocytes, cytokeratin and vimentin antigens expression, and modified one step silver stain to identify the Argyrophilic nucleolar organizer regions (AgNors) for evaluation of the proliferative potentiality of the tumor. Blood samples of five normal individuals were considered as controls. Histopathologic examination demonstrated epithelial variant in 12 cases, mixed (biphasic) variant in 4 cases and 2 cases were sarcomatoid. Flowcytometric analysis exhibited a significant increase in the mean percentage of circulating CD4+ T cell count in mesothelioma (56.7% +/- 6.99) versus control (43% +/- 1.58), p < 0.001. In contrast, cytotoxic CD8+ cells were significantly reduced (p < 0.001) in comparison to the control (25.2% +/- 2.96 versus 32% +/- 4.6 respectively). CD4/CD8 ratio was significantly increased versus control (2.06 +/- 0.57 versus 1.3 +/- 0.02 p < 0.05). Intratumoral CD8+ lymphocytes were depleted in mesothelioma cases. There was significant reduction of circulating cytotoxic T lymphocytes (CTL) in relation to mixed and sarcomatoid variants versus epithelial differentiation (mean = 25.25 +/- 4.86, 22 +/- 1.41 and 29.5 +/- 9.9 respectively with a p value < 0.05). Reduction of cytotoxic T cells was also associated with increased expression of vimentin and increased proliferative activity which has been identified by increased AgNors in mixed and sarcomatoid differentiation. In conclusion, mesothelioma might be associated with modulation of the tumoricidal effect of cytotoxic T lymphocytes in relation to tumor differentiation and its proliferative potentiality. Immunophenotyping analysis of leukocytes may reflect the competence of immune system against malignancy and act as an additive prognostic parameter for mesothelioma progression and probably expecting response to oncotherapy protocols.