The identification of the most appropriate T-cell subset to ensure optimal persistence and anti-tumor activity is a major goal of cancer immunotherapy. We identified a novel post-mitotic CD45RA+CD62L+ T cell subpopulation (TTN), generated in vitro upon activation of nave T (TN) cells with beads conjugated to anti-CD3 and anti-CD28 antibodies. This cell population is highly proliferative, produces low levels of IFNg and cytotoxic molecules, and requires IL-7 and IL-15 for in vitro expansion.
IL-7 and IL-15 instruct the generation of human memory stem T cells from naive precursors.
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Requirement for the histone deacetylase Hdac3 for the inflammatory gene expression program in macrophages.
Specimen part, Treatment
View SamplesPan-Hdac inhibitors (HDACi) are endowed with a potent anti-inflammatory activity, but the relative role of each of the eleven Hdac proteins sensitive to HDACi to the inflammatory gene expression program is unknown. Using an integrated genomic approach we found that Hdac3-deficient macrophages are unable to activate almost half of the inflammatory gene expression program when stimulated with lipopolysaccharide (LPS). A large part of the activation defect is due to loss of basal and LPS-inducible expression of IFNb, which in basal cells maintains Stat1 protein levels, and after stimulation acts in an autocrine/paracrine manner to promote a secondary wave of Stat1-dependent gene expression. We show that loss of Hdac3-mediated repression of nuclear receptors leads to hyperacetylation of thousands of genomic sites and associated gene derepression. The upregulation of the constitutively expressed prostaglandin endoperoxide synthase, Ptgs1 (Cox-1), has a causative role in the phenotype, since its chemical inhibition reverts the Ifnb activation defect. These data may have relevance for the use of selective Hdac inhibitors as anti-inflammatory agents.
Requirement for the histone deacetylase Hdac3 for the inflammatory gene expression program in macrophages.
Specimen part, Treatment
View SamplesTo investigate the impact of the iNKT cells on the tumor-infiltrating leukocytes in TRAMP mouse prostate cancer.
Bimodal CD40/Fas-Dependent Crosstalk between iNKT Cells and Tumor-Associated Macrophages Impairs Prostate Cancer Progression.
Age, Specimen part
View SamplesSmall nucleolar RNAs (snoRNAs) and small Cajal body-specific RNAs are non-coding RNAs involved in the maturation of other RNA molecules. Alterations of sno/scaRNA expression may play a role in cancerogenesis. This study elucidates the patterns of sno/scaRNA expression in highly purified cells from 211 chronic lymphocytic leukemia (CLL) patients (Binet stage A) also in comparison with those of different normal B-cell subsets. CLLs display a sno/scaRNAs expression profile similar to normal memory, nave and marginal-zone B-cells, with the exception of a few down-regulated transcripts (SNORA31, -6, -62, and -71C). Our analyses also suggest some heterogeneity in the pattern of sno/scaRNAs expression which is apparently unrelated to the major biological (ZAP-70 and CD38), molecular (IGHV mutation) and cytogenetic markers. Moreover, we found that SNORA70F was significantly down-regulated in poor prognostic subgroups and this phenomenon was associated with the down-regulation of its host gene COBLL1. Finally, we generated an independent model based on SNORA74A and SNORD116-18 expression, which appears to distinguish two different prognostic CLL groups. These data extend the view of sno/scaRNAs deregulation in cancer and may contribute to discover novel biomarkers associated with the disease and potentially useful to predict the clinical outcome of early stage CLL patients.
Small nucleolar RNAs as new biomarkers in chronic lymphocytic leukemia.
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View SamplesBackground: Zidovudine remains the cornerstone drug for prophylaxis to prevent mother-to-child HIV-1 transmission. A mild but long-lasting hematological multilineage defect is observed in children exposed in utero.
Genotoxic signature in cord blood cells of newborns exposed in utero to a Zidovudine-based antiretroviral combination.
Specimen part, Treatment
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Association between gene and miRNA expression profiles and stereotyped subset #4 B-cell receptor in chronic lymphocytic leukemia.
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View SamplesHighly homologous B-cell receptors, stereotyped BCR, are expressed in a recurrent fraction of patients with chronic lymphocytic leukemia (CLL). In this study, we investigated the biological and molecular features of leukemic cells from 16 patients utilizing stereotyped subset #4 BCR (IGHV4-34) in a prospective cohort of 462 Binet stage A CLL patients. All subset #4 patients were characterized by the IGHV mutated gene configuration and by the absence of unfavorable cytogenetic lesions, and NOTCH1 and SF3B1 mutations. Gene expression profiling demonstrated a significant downregulation of WDFY4, MF2A and upregulation of PDGFA, FGFR1 and TFEC genes in leukemic cells from subset #4 compared to those from the remaining IGHV-mutated patients. Similarly, in the cells from subset #4 cases there was a specific miRNA expression pattern involving the upregulation of miR-497 and miR-29c. Furthermore transfection of miR-497 mimic in primary leukemic CLL cells induced a downregulation of BCL2, known to be a validated target of this miRNA. Our data identify a distinct gene and miRNA expression profile of the cells from subset #4 patients, providing further evidence for the putative role of BCR in shaping the features of the leukemic cells.
Association between gene and miRNA expression profiles and stereotyped subset #4 B-cell receptor in chronic lymphocytic leukemia.
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Clinical monoclonal B lymphocytosis versus Rai 0 chronic lymphocytic leukemia: A comparison of cellular, cytogenetic, molecular, and clinical features.
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View SamplesProspective series of 136 clinical monoclonal B lymphocytosis (cMBL) and 216 chronic lymphocytic leukemia (CLL) Rai 0 patients, were investigated in this study. While the distribution of CD38 and ZAP-70 positivity was similar, IGHV-mutated cases were more frequent among cMBL (P = 0.005). A Cox multivariate analysis on the whole patient cohort showed that cMBL condition was predictive of longer PFS, while CD38 expression and IGHV-unmutated status and CD38 expression correlated significantly with a shorter PFS in cMBL and Rai0-CLL, respectively. Trisomy 12, 11q- and 17p- abnormalities were scanty and of no predictive value in both conditions. Notably, gene and miRNA expression profiling showed no significant differences between cMBL and Rai0-CLL. Furthermore, similar gene and miRNA expression signatures were found in cMBL and Rai0-CLL according to the IGHV gene mutational status: that is, unmutated cases had different signatures from mutated cases, irrespectively of the cMBL or CLL condition. Overall, our study based on a prospective series of patients indicates that no major biological differences exist in cMBL compared to Rai0-CLL, suggesting that this two entities mainly differ for the initial size of the monoclonal cell population which may reflect in the longer time for clonal expansion.
Clinical monoclonal B lymphocytosis versus Rai 0 chronic lymphocytic leukemia: A comparison of cellular, cytogenetic, molecular, and clinical features.
No sample metadata fields
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