Reduced efficacy of multiple doses of CpG-matured dendritic cell tumor vaccine in an experimental model.

CpG motifs have been advanced as agents that stimulate the maturation of DCs for immunotherapy. The present study tested the hypothesis that multiple doses of CpG-matured DC vaccine would be efficacious for complete eradication of experimentally-induced tumor. Accordingly, WEHI164 cells were implanted subcutaneously in the flank of BALB/c mice. During DC culture, tumor lysate was added to immature DCs followed by addition of CpG or non-CpG control 4-6h later. A total of three doses of CpG or non-CpG control-matured DCs were injected around tumors. The results showed that multiple doses of CpG-matured DCs led to considerable decrease in cytotoxicity of lymphocytes and significantly increased tumor growth rate compared to a single dose. Further, mice which received three doses of the vaccine also displayed significant FoxP3 in tumor tissue. In conclusion, multiple doses of CpG-matured DCs exhibited decreased anti-tumor immunity in association with increased expression of FoxP3.

Chronic inflammation and oxidative stress as a major cause of age-related diseases and cancer.

Chronic inflammation is a pathological condition characterized by continued active inflammation response and tissue destruction. Many of the immune cells including macrophages, neutrophils and eosinophils are involved directly or by production of inflammatory cytokine production in pathology of chronic inflammation. From literatures, it is appear that there is a general concept that chronic inflammation can be a major cause of cancers and express aging processes. Moreover, many studies suggest that chronic inflammation could have serious role in wide variety of age-related diseases including diabetes, cardiovascular and autoimmune diseases. Inflammatory process induces oxidative stress and reduces cellular antioxidant capacity. Overproduced free radicals react with cell membrane fatty acids and proteins impairing their function permanently. In addition, free radicals can lead to mutation and DNA damage that can be a predisposing factor for cancer and age-related disorders. This article reviews the antioxidant defense systems, free radicals production and their role in cancer and age related diseases and also some of the recent patent relevant to the field. Study of the role of free radicals in human diseases can help the investigators to consider the antioxidants as proper agents in preventive medicine, especially for cancer and aging processes.

Effect of high dose natural ionizing radiation on the immune system of the exposed residents of Ramsar Town, Iran.

Iran is one of several countries that has regions of high dose natural ionizing radiation. Two well-known villages in the suburb of Ramsar Town in the Caspian Sea strip, Taleshmahaleh and Chaparsar, have background radiation that is 13 times higher than normal. This radiation is the result of Radium 226 and Radon gas both of which are highly water soluble. While people living in these regions do not suffer from any major health problems, we decided to study the their immune responses to infection and inflammation in order to determine if their habitat affects their immune defense mechanisms as a way of compensating for their exposure to high dose environmental ionizing radiation. Our results showed that the total serum antioxidant level in the exposed people was significantly lower than the individuals not exposed to high dose natural ionizing radiation. The exposed individuals also had higher lymphocyte-induced IL-4 and IL-10 production, and lower IL-2 and IFN-gamma production. In addition, neutrophil NBT, phagocytosis, and locomotion were higher in the exposed group. In contrast, lymphocyte proliferation in response to PHA was unaffected. We conclude that the immune system of individuals exposed to high dose ionizing radiation has adapted to its environment by shifting from a Type 1 to a Type 2 response to promote anti-inflammation. This may be because inflammatory Type 1 responses generate more free radicals than Type 2 responses, in addition to the free radicals generated as a result of high environmental radiation. Thus, the serum total antioxidant level in the exposed residents was lower than the unexposed group.