Search

As long as breast cancer (BC) stays under immunosurveillance, it can be controlled by treatments eliciting anticancer immune responses. However, once BC escapes immunosurveillance, it becomes therapeutically uncontrollable. A paper in the Journal for ImmunoTherapy of Cancer describes a new hormone receptor-positive BC cell line generating incurable tumors in C57BL/6 mice. [ABSTRACT FROM AUTHOR]

Macrophages play crucial roles in atherosclerotic immune responses. Recent investigation into macrophage autophagy (AP) in atherosclerosis has demonstrated a novel pathway through which these cells contribute to vascular inflammation. AP is a cellular catabolic process involving the delivery of cytoplasmic contents to the lysosomal machinery for ultimate degradation and recycling. Basal levels of macrophage AP play an essential role in atheroprotection during early atherosclerosis. However, AP becomes dysfunctional in the more advanced stages of the pathology and its deficiency promotes vascular inflammation, oxidative stress, and plaque necrosis. In this paper, we will discuss the role of macrophages and AP in atherosclerosis and the emerging evidence demonstrating the contribution of macrophage AP to vascular pathology. Finally, we will discuss how AP could be targeted for therapeutic utility. [ABSTRACT FROM AUTHOR]

NF-κB regulates inflammatory and immune response by increasing the expression of specific genes. In celiac disease proinflammatory cytokines, adhesion molecules, and enzymes whose gene expression is known to be regulated by NF-κB are involved. This study investigated the activation of NF-κB in inflamed mucosa from patients with untreated celiac disease. Biopsy specimens from control, untreated, and treated patients were subjected to molecular biology analysis. NF-κB activation was evaluated by electrophoretic mobility shift assay. NF-κB related subunit protein level, and inducible nitric oxide synthase and cyclo-oxygenase 2 protein expression was analyzed by western blot. Both NF-κB/DNA binding activity and p50/p65 nuclear levels were higher in biopsy specimens from untreated patients than in those from treated patients and controls. The degradation of IκBβ in the cytosol and the reappearance in the nucleus indicated a persistent NF-κB activation in celiac disease. NF-κB activity was maintained in cultured biopsy specimens up to 6 h and decreased at 24 h, and then the addition of peptic-tryptic digest of gliadin caused the recovery of NF-κB activity at 6 h. NF-κB/DNA binding activity was correlated with inducible nitric oxide synthase and cyclo-oxygenase-2 protein expression. These results show for the first time that NF-κB is activated in the inflamed mucosa of celiac patients and suggest that it may represent a molecular target for the modulation of inflammatory response in celiac disease. [ABSTRACT FROM AUTHOR]

The success of chemotherapy largely depends on the anticancer immune response triggered by tumor cells that succumb to immunogenic cell death (ICD). One of the hallmarks of ICD is premortem autophagy that facilitates the release of adenosine triphosphate from dying cancer cells and acts as a chemoattractant for dendritic cell precursors. Here, we show that the immune response induced by inoculation of cancer cells undergoing ICD in response to the anthracycline mitoxantrone (MTX) can be improved by a short-term fasting regimen (48 hours of starvation) and that this effect is reversed by systemic administration of the autophagy inhibitor dimethyl α-ketoglutarate. Tumor growth reduction by MTX treatment is known to depend on autophagy induction in cancer cells as well as on an intact immune system. We compared the antitumor effects of MTX on autophagy-competent cancers implanted in wild type (WT) or partially autophagy-deficient (Becn1± or Atg4b−/-) mice. While there was no difference in the tumor growth reducing effects of MTX on tumors evolving in WT, Becn1+/- and Atg4b−/- mice, we observed an increase in the toxicity of MTX on Atg4b−/- mice. These results suggest that autophagy in cancer cells (but less so in host cells) is rate-limiting for therapeutically relevant anticancer immune responses, yet has a major role in blunting the life-threatening toxicity of chemotherapy. [ABSTRACT FROM AUTHOR]