CCL2 producton in neutrophils (PMN) from peripheral blood of hepatocellular carcinoma patients (49.1)

Abstract

Abstract An immunosuppressive subset of PMN has recently been demonstrated in mice with severe immunocompromised status such as severe systemic inflammatory response syndrome (SIRS), severe thermal injury or severe stress. By CCL2 production, these PMN direct resident macrophages (MƒÓ) to M2MƒÓ. Functional deficiencies of tumor-associated immune cells have been shown in cancer patients bearing acceleration of tumor growth who are known to be immunocompromised hosts. Hepatocellular carcinoma (HCC) was one of a most frequent malignant tumor in worldwide. Repeated episodes of recurrence and metastasis are commonly associated with the poor prognosis of HCC. Therefore, in this study, subsets of PMN from HCC patients were immunobiologically investigated. Thirty HCC patients admitted to Osaka Medical College were randomly enrolled. PMNs were isolated from heparinized peripheral blood using Ficoll-Hypaque and dextran sedimentation. PMNs from 5 healthy donors were used as controls. PMN (1 x 106 cells/ml) were stimulated with 0.0075% SAC for 24 hrs. Culture fluids harvested were assayed for CCL2 by ELISA. After SAC stimulation, CCL2 were produced by all patient PMNs, while none of healthy donor PMNs produced these soluble factors. Moreover, CCL2 production was significantly increased in proportion to tumor size or extent. These results suggest that PMN with a function to produce CCL2 are predominated in HCC patients and they may be involved in their poor prognosis.