| IntroductionAccording to the cancer statistics made by American Cancer Society, the relative five-survival rate of ovarian cancer increased gradually from 1970 to 2000. However, the cure rate of advanced ovarian cancer is still low in 20%-25% because of the high relapse, which usually occur in the peritoneal cavity. Searching for the reasons, researchers have found that there existed severe immune dysfunction in peritoneal cavity of patients with ovarian cancer.Macrophages are the main executors of innate immune and important regulators of acquired immune, playing an important role in the immunologic defense against cancer. Its antitumor activities include (1) the phagocytosis and subsequent degradation of live and dead neoplastic cells; (2) the cytotoxicity against neoplastic cells; (3) the secretion of biologic active molecules; (4) the presentation of tumor antigens to T lymphocytes. However, tumor-associated macrophages derived from ovarian cancers were found to exist severe deficient of antitumor activities, which were proved that:(l) had a limited antitumor cytotoxicity; (2) did not release substantial amount of TNF, IL-1, but release high amount of immunosuppressive cytokines, including TGF-p, IL-10; (3) although had no previous reports about its antigen-presenting function in ovarian cancer, whichwas confirmed to be inhibited in other cancer types.It has been found that the main reasons resulting in macrophages functional deficient included the inhibitory bioactive factors released from cancer cells, the ischemia circumstances, the application of cytotoxic drugs and the undernourished states. However, more and more evidences revealed that the styles of cell death would affect immune activities of macrophages profoundly.It has shown that far from neutral in immunological term, clearance of apoptotic cells by phagocytes can result in powerful anti-inflammatory and immunosuppressive effects in inflammatory and autoimmune diseases. Apoptotic cells, co-cultured with human macrophages, inhibited the production of TNF- , IL- , and IL-12, but promoted the synthesis of TGF- and IL-10, which were known to inhibit immune response. However, necrotic cells stimulated inflammatory progression by enhancing the production of TNF- , IL-10, and IL-12 by macrophages. Relative studies in neoplasm were limited. Previous studies on hematological malignance and colorectal cancer revealed that macrophages co-cultured with necrotic tumor cells greatly enhanced their competence to get rid of tumor cells, while those co-cultured with apoptotic cells showed not only decreased competence in clearance, but promoted the growth of tumor cells. Faced with the researches upsurging of anti-inflammatory death and clearance, there were also evidences that the clearance of apoptotic cells can activate macrophages. Some researchers revealed that apoptosis could stimulate pro-inflammatory response by macrophages secretion of TNF, IL-land IL-18. There were also evidences showed that apoptotic, but not necrotic tumor cell vaccines, induced a potent immune response in vivo.Chemotherapy is the main therapeutic choice after operation in the patients with advanced ovarian cancer. Although it has long been thought that the ultimate result of anti-cancer drugs was cellular necrosis, the primary mechanism by which most anti-cancer drugs induce cell death is apoptosis. Many cytostatic drugs with widelydifferent modes of action have shown to induce apoptosis in sensitive ovarian cell. In addition to the ischemia circumstances and immune injury, researches have proved that there were much higher amounts of apoptotic tumor cells existing in ovarian cancer sites and ascites, special after chemotherapy than normal controls. Whether and how do the apoptotic ovarian cancer cells affect antitumor immune of macrophages? Should the apoptotic ovarian cancer cells be responsible for the functional deficient of tumor-associated macrophages? The aim of this study was therefore to investigate the effects of apoptotic and necrotic ovarian cance... |
PDF Full Text Request