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Abstract: Metastatic cancer is usually an incurable disease. Cancers have a broad repertoire of subversive tactics to defeat the immune system. They mimic self, they down-regulate MHC molecules so that T cells are blind to their presence, they interfere with antigen presentation, and they produce factors that can kill T cells or paralyze their response to antigens. Furthermore, the same powerful machinery designed to prevent harmful autoimmune responses is also acting to protect cancers. In particular, cancer is protected with the help of so-called regulatory immune cells. These unique subsets of cells, represented by almost every immune cell type, function to control responses of effector immune cells. In this review, we will discuss the evidence that cancer actively promotes cross-talk of regulatory immune cells to evade immunosurveillance. We will also discuss the role of a newly described cell type, regulatory B cells, by emphasizing their importance in suppression of antitumor immune responses. Thus, cancer not only directly suppresses immune function, but also recruits components of the immune system to become traitors and protect the tumor from immune attack. [Copyright &y& Elsevier]

The chemokine/chemokine receptor network is an essential part of an intricate system of immunosurveillance and homeostasis, it promotes or suppresses neovascularization, affects and regulates directly or indirectly growth and metastasis of malignant cells. Numerous studies have been conducted to harness this network as therapeutic agents for cancer to redress the chemokine balance and control angiogenesis and tumour growth and metastasis. Second generation of immunotherapeutics and chemoattractant-based vaccines use chemokines and chemoattractant peptides to elicit antitumor immunity by a specific targeting and modulating subsets of effector leukocytes, including professional antigen presenting cells. [Copyright &y& Elsevier]

Highlights • Down Syndrome is manifested by overproduction of Aβ and hyperphosphorylated tau. • Anti-Aβ immunization reduces microglial and astroglial inflammatory phenotype. • Vaccination facilitates clearance of Aβ oligomers and small inclusion of Aβ from the neural tissue. • Vaccinated Ts65Dn performed better in spatial learning and short-term memory tasks. • DS individuals may benefit from active immunotherapy against Aβ from a young age. Abstract Down Syndrome (DS), the most common cause of genetic intellectual disability, is characterized by over-expression of the APP and DYRK1A genes, located on the triplicated chromosome 21. This chromosomal abnormality leads to a cognitive decline mediated by Amyloid-β (Aβ) overproduction and tau hyper-phosphorylation as early as the age of 40. In this study, we used the Ts65Dn mouse model of DS to evaluate the beneficial effect of a DNA vaccination against the Aβ 1-11 fragment, in ameliorating Aβ-related neuropathology and rescue of cognitive and behavioral abilities. Anti-Aβ 1-11 vaccination induced antibody production and facilitated clearance of soluble oligomers and small extracellular inclusions of Aβ from the hippocampus and cortex of Ts65Dn mice. This was correlated with reduced neurodegeneration and restoration of the homeostatic phenotype of microglial and astroglial cells. Vaccinated Ts65Dn mice performed better in spatial-learning tasks, exhibited reduced motor hyperactivity typical for this strain, and restored short-term memory abilities. Our findings support the hypothesis that DS individuals may benefit from active immunotherapy against Aβ from a young age by slowing the progression of dementia. [ABSTRACT FROM AUTHOR]

Abstract: Regulatory T cells (Tregs) and beta-galactoside-binding protein (βGBP), a regulatory protein often found expressed at sites of immunological privilege, have similar functions. Their presence affects the outcome of harmful autoimmunity and cancers, including experimental autoimmune encephalomyelitis and malignant gliomas. Here we report a novel pathway by which Tregs express and utilize βGBP to control CD8+ T cell responses partially activating TCR signaling but blocking PI3K activity. As a result, this leads to a loss of p21ras, ERK and Akt activities despite activation of TCR proximal signals, such as phosphorylation of CD3ζ, Zap70, Lat and PKCθ. Although non-processive TCR signaling often leads to cell anergy, Tregs/βGBP did not affect cell viability. Instead, βGBP/Tregs transiently prevented activation of CD8+ T cells with self-antigens, while keeping their responses to xenogeneic antigens unaffected. [Copyright &y& Elsevier]