Dendritic cell-based immunotherapy: a promising approach for treatment of cancer

The accumulating evidence in favor of tumor immunosurveillance indicates that immunotherapies may prove effective for the treatment of cancer. Many current approaches against cancer immunotherapy are often limited in their potential to induce effective anti-tumor immune responses. However, recent approach with dendritic cell based therapy proves to be an effective method for induction of anti-tumor immune response. In this review we discuss the effectiveness and complications associated with DC based immunotherapy and new strategies being perused for effective anti cancer response

Comparative study of adenosine deaminase activity, insulin resistance and lipoprotein(a) among smokers and healthy non-smokers

Background: Adenosine deaminase also known as adenosine aminohydrolase involved in purine metabolism. Its primary function is development and maintenance of immune system. The main objective of the study was to estimate adenosine deaminase (ADA) enzyme and find its correlation with lipoprotein(a) and insulin resistance among smokers and healthy non-smokers.Methods: Fifty smokers and fifty healthy non-smokers were selected based on WHO definition. ADA, lipid profile and glucose was estimated on a fully automated analyser by IFCC approved methods and lipoprotein(a) was done by latex enhanced immune-turbidimetric assay method respectively.Results: After appropriate screening ADA activity and insulin was significantly elevated among smokers when compared with healthy non-smokers. A positive correlation was found between pack size of cigarette and ADA activity and also with Lp(a) respectively. In addition, there was no correlation between serum lipid profile and ADA activity.Conclusions: Adenosine deaminase activity was increased in patients in response to nicotine which is the key component of cigarette smoke. These findings indicate that nicotine and carbon monoxide can alter lipoprotein synthesis and also modify LDL to oxidized form which can lead to ischemic heart disease

Increased IL-23 secretion and altered chemokine production by dendritic cells upon CD46 activation in patients with multiple sclerosis

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Effect of mouse recombinant leptin on ethanol elicited damage in the mouse hepatocellular carcinoma cell lines

A BSTRACT Obesity is associated with hepatocellular carcinoma (HCC). Leptin, an anti-obesity hormone exerts potent modulatory properties both in vivo and in vitro. We have previously shown the reduction of lipotoxicity with leptin in vivo. The aim of this study was to evaluate the effect of leptin on ethanol induced fibrogenesis and apoptosis in mouse hepatocellular carcinoma (HCC) cell lines. Mouse HCC cell lines were treated for 48 h with and without ethanol (500 mM) and leptin (31.2 nM), subsequently analyzed for cell proliferation, flow cytometry, biochemical and molecular studies. Ethanol exposure significantly reduced the cell viability as evidenced by 3-(4,5 dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay (P<0.05). Moreover, ethanol treated cells significantly lowered DNA synthesis as evidenced by thymidine incorporation (P<0.05) and increased DNA fragmentation. Ethanol incubation also significantly increased the % of apoptotic cells (P<0.05). These results were compared with that of untreated control cell lines. Leptin co-treatment with ethanol significantly enhanced (P<0.05) cell viability and DNA synthesis, whereas significantly (P<0.05) decreased apoptotic cells and DNA ladder formation. In addition, ethanol exposure significantly (P<0.05) increased cytokine (TNFα), reactive oxygen species (ROS),TBARS and mRNA expressions of caspase-3, procollagen type I, MMP 2, MMP 9 and TIMP-1 compared to untreated control mouse HCC cell lines. Leptin co-administration significantly (P<0.05) down regulated the above indices when compared to ethanol alone exposed mouse HCC cell lines. Furthermore, ethanol exposure significantly (P<0.05) lowered antioxidant enzymes activities. Leptin co-administration along with ethanol significantly (P<0.05) improved antioxidant enzymes activities. Thus, our experimental data provide evidence that leptin treatment to ethanol exposed mouse HCC cell lines results in attenuating fibrogenesis and apoptosis, thereby warranting further population based mechanistic studies

CD40-Induced countercurrent conduits for tumor escape or elimination?

CD40 - which is expressed on endothelial cells and antigen-presenting cells, such as B cells, macrophages and dendritic cells - is a glycoprotein receptor for T cell-expressed CD40-ligand. CD40 signaling leads to production of both pro-inflammatory and anti-inflammatory mediators. Some of these mediators, such as vascular endothelial growth factor, help in angiogenesis, forming new capillaries. Although these capillaries can function as conduits for tumor-cell metastasis, these same vessels can also be a gateway for entry of activated anti-tumor effector cells that eliminate tumors. How such countercurrent processes can be turned in favor of anti-tumor immunity remains to be shown

Reversal of tumor induced dendritic cell paralysis: a treatment regimen against cancer

Dendritic cells (DC) are the most potent antigens presenting cells with the capacity to stimulate naive T cells and induce primary and secondary immune responses. Due to these features DC have been exploited for vaccine delivery in an attempt to actively immunize cancer patients, but the vaccine- induced immune responses have achieved partial success but are not yet sufficient to attain robust and durable therapeutic effect in cancer patients. The partial failure of current vaccine formulations are explained by the extraordinary complexity of the immune response, which makes the task of exploiting the potential of such a therapeutic approach highly challenging. Overall findings obtained from the clinical observations in human suggest that immune system can be polarized against tumor cells by means of DC mediated vaccine. It is clear that there are complex interactions between tumor cells and DC, through their inhibitory effect on DC tumor cells may negatively regulate priming tumor specific immunity. The complete eradication of tumor is possible only when we gain the thorough understanding of DC biology and its interaction with tumor before we design any vaccine formulations using dendritic cells. This review will summarize the recent advances in understanding the role of DC in the regulation of innate and adaptive anti-tumor immunity, and tumor- induced DC paralysis as a major mechanism by which tumors escape host immune response. Knowledge on these aspects will provide important implications for developing more effective DC mediated vaccination against tumor

Differential CD40/CD40L expression results in counteracting antitumor immune responses

Establishment of host-protective memory T cells against tumors is the objective of an antitumor immunoprophylactic strategy such as reinforcing T cell costimulation via CD40-CD40L interaction. Previous CD40-targeted strategies assumed that T cell costimulation is an all-or-none phenomenon. It was unknown whether different levels of CD40L expression induce quantitatively and qualitatively different effector T cell responses. Using mice expressing different levels of CD40L, we demonstrated that the greater the T cell CD40L expression the less tumor growth occurred; the antitumor T cell response was host-protective. Lower levels of CD40L expression on T cells induced IL-10-mediated suppression of tumor-regressing effector CD8+ T cells and higher productions of IL-4 and IL-10. Using mice expressing different levels of CD40 or by administering different doses of anti-CD40 Ab, similar observations were recorded implying that the induction of protumor or antitumor T cell responses was a function of the extent of CD40 cross-linking. IL-10 neutralization during priming with tumor Ags resulted in a stronger tumor-regressing effector T cell response. Using IL-10-/- DC for priming of mice expressing different levels of CD40L and subsequent transfer of the T cells from the primed mice to nu/nu mice, we demonstrated the protumor role of IL-10 in the induction of tumor-promoting T cells. Our results demonstrate that a dose-dependent cross-linking of a costimulatory molecule dictates the functional phenotype of the elicited effector T cell response. The T cell costimulation is a continuum of a function that induces not only graded T cell responses but also two counteracting responses at two extremes