Development of Exhaustion and Acquisition of Regulatory Function by Infiltrating CD8+CD28- T Lymphocytes Dictate Clinical Outcome in Head and Neck Cancer.

Head and neck squamous cell carcinoma (HNSCC) has a poor clinical outcome despite the presence of a rich CD8+ T cell tumor infiltrate in the majority of patients. This may be due to alterations of tumor infiltrating CD8+ T cells. Here, we performed a characterization of HNSCC infiltrating CD8+ T cells in a cohort of 30 patients. The results showed that differential intratumoral frequency of CD8+CD28+ T cells, CD8+CD28- T cells, and CD8+CD28-CD127-CD39+ Treg distinguished between HNSCC patients who did or did not respond to treatment. Moreover, high PD1 expression identified a CD8+CD28- T cell subpopulation, phenotypically/functionally corresponding to CD8+CD28-CD127-CD39+ Treg, which showed a high expression of markers of exhaustion. This observation suggests that development of exhaustion and acquisition of regulatory properties may configure the late differentiation stage for intratumoral effector T cells, a phenomenon we define as effector-to-regulatory T cell transition.

Chromosomal Localization of 18S-28S rDNA and (TTAGGG)n Sequences in Two South African Dormice of the Genus Graphiurus (Rodentia: Gliridae).

Classical cytogenetics and mapping of 18S-28S rDNA and (TTAGGG)n sequences by fluorescence in situ hybridization (FISH) was performed on Graphiurus platyops (GPL) and Graphiurus ocularis (GOC) metaphases with the aim to characterize the genomes. In both species, inverted DAPI karyotypes showed the same diploid number, 2n = 46, and hybridization of the (TTAGGG)n probe revealed interstitial telomeric sequences (ITSs) at the centromeres of almost all bi-armed chromosomes. FISH with the rDNA probe localized nucleolus organizer regions (NORs), at the terminal ends of the p arms of the subtelocentric pairs 16 and 17 in both species and detected additional signals on GPL8 and GOC18, 19, and 22. The species have similar karyotypes, but their chromosome pairs 18-22 differ in morphology; these are acrocentric in G. platyops, as also confirmed by C-banding, and subtelocentric in G. ocularis. These differences in pairs 18-22 were also highlighted by hybridization of the telomeric probe (TTAGGG)n, which showed the small p arms in G. ocularis enriched with ITSs. FISH of rDNA probes detected multiple NOR loci in G. ocularis, underlining the intense evolutionary dynamics related to these genes. Although the Graphiurus species analyzed have similar karyotypes, the results on the repetitive sequences indicate a complex pattern of genomic reorganization and evolution occurring in these phylogenetically close species.

Ci8 short, a novel LPS-induced peptide from the ascidian Ciona intestinalis, modulates responses of the human immune system.

The selective modulation of immunity is an emerging concept driven by the vast advances in our understanding of this crucial host defense system. Invertebrates have raised researchers' interest as potential sources of new bioactive molecules owing to their antibacterial, anticancer and immunomodulatory activities. A LipoPolySaccharide (LPS) challenge in the ascidian Ciona intestinalis generates the transcript, Ci8 short, with cis-regulatory elements in the 3' UTR region that are essential for shaping innate immune responses. The derived amino acidic sequence in silico analysis showed specific binding to human Major Histocompatibility Complex (MHC) Class I and Class II alleles. The role of Ci8 short peptide was investigated in a more evolved immune system using human Peripheral Blood Mononuclear Cells (PBMCs) as in vitro model. The biological activities of this molecule include the activation of 70kDa TCR ζ chain Associated Protein kinase (ZAP-70) and T Cell Receptor (TCR) Vß oligo clonal selection on CD4+ T lymphocytes as well as increased proliferation and IFN-γ secretion. Furthermore Ci8 short affects CD4+/CD25high induced regulatory T cells (iTreg) subset selection which co-expressed the functional markers TGF-ß1/Latency Associated Protein (LAP) and CD39/CD73. This paper describes a new molecule that modulates important responses of the human adaptive immune system.

Partially Purified Extracts of Sea Anemone Anemonia viridis Affect the Growth and Viability of Selected Tumour Cell Lines.

In the last few years, marine species have been investigated for the presence of natural products with anticancer activity. Using reversed phase chromatography, low molecular weight proteins were fractionated from the sea anemone Anemonia viridis. Four different fractions were evaluated for their cytotoxic activity by means of erythrocyte haemolysis test, MTS, and LDH assays. Finally, the antiproliferative activities of three of these fractions were studied on PC3, PLC/PRF/5, and A375 human cancer cell lines. Our analysis revealed that the four fractions showed different protein contents and diverse patterns of activity towards human PBMC and cancer cell lines. Interestingly, fractions III and IV exerted cytotoxic effects on human cells. Conversely, fractions I and II displayed very low toxic effects associated with antiproliferative activities on cancer cell lines.

Hydroxytyrosol modulates Par j 1-induced IL-10 production by PBMCs in healthy subjects.

Several papers have demonstrated the importance of substances from natural sources which can exert powerful anti-inflammatory effects. In this respect, hydroxytyrosol, one of the major elements of the phenolic components of olive oil, has been extensively studied for its anti-inflammatory activities and safety profile. In this report, we demonstrate that the co-stimulation of human PBMCs from healthy subjects with the Par j 1 allergen and hydroxytyrosol induced a statistically significant increase in the amount of Par j 1-induced IL-10, demonstrating that hydroxytyrosol can modulate an allergen-specific immune response potentiating a suppressive immune response towards an allergen. Our work opens the way to further studies to elaborate the possibility of using hydroxytyrosol as a nutrient for allergy prevention.