246 research outputs found
Role of distinct natural killer cell subsets in anticancer response
No full textNatural killer (NK) cells, the prototypic member of innate lymphoid cells, are important
effectors of anticancer immune response. These cells can survey and control tumor
initiation due to their capability to recognize and kill malignant cells and to regulate the
adaptive immune response via cytokines and chemokines release. However, several
studies have shown that tumor-infiltrating NK cells associated with advanced disease can
have profound functional defects and display protumor activity. This evidence indicates
that NK cell behavior undergoes crucial alterations during cancer progression. Moreover,
a further level of complexity is due to the extensive heterogeneity and plasticity of these
lymphocytes, implying that different NK cell subsets, endowed with specific phenotypic
and functional features, may be involved and play distinct roles in the tumor context.
Accordingly, many studies reported the enrichment of selective NK cell subsets within
tumor tissue, whereas the underlying mechanisms are not fully elucidated. A malignant
microenvironment can significantly impact NK cell activity, by recruiting specific subpopulations
and/or influencing their developmental programming or the acquisition of a
mature phenotype; in particular, neoplastic, stroma and immune cells, or tumor-derived
factors take part in these processes. In this review, we will summarize and discuss the
recently acquired knowledge on the possible contribution of distinct NK cell subsets in
the control and/or progression of solid and hematological malignancies. Moreover, we
will address emerging evidence regarding the role of different components of tumor
microenvironment on shaping NK cell response
Hyperthermia enhances CD95-ligand gene expression in T lymphocytes
No full textHyperthermia represents an interesting therapeutic strategy for the treatment of tumors. Moreover, it is able to regulate several aspects of the immune response. Fas (APO-1/CD95) and its ligand (FasL) are cell surface proteins whose interaction activates apoptosis of Fas-expressing targets. In T cells, the Fas-Fas-L system regulates activation-induced cell death, is implicated in diseases in which lymphocyte homeostasis is compromised, and plays an important role during cytotoxic and regulatory actions mediated by these cells. In this study we describe the effect of hyperthermia on activation of the fas-L gene in T lymphocytes. We show that hyperthermic treatment enhances Fas-L-mediated cytotoxicity,fas-L mRNA expression, and fas-L promoter activity in activated T cell lines. Our data indicate that hyperthermia enhances the transcriptional activity of AP-1 and NF-kappaB in activated T cells, and this correlates with an increased expression/nuclear translocation of these transcription factors. Moreover, we found that heat shock factor-1 is a transactivator of fas-L promoter in activated T cells, and the overexpression of a dominant negative form of heat shock factor-1 may attenuate the effect of hyperthermia on fas-L promoter activity. Furthermore, overexpression of dominant negative mutants of protein kinase Cepsilon (PKCepsilon) and PKCtheta partially inhibited the promoter activation and, more importantly, could significantly reduce the enhancement mediated by hyperthermia, indicating that modulation of PKC activity may play an important role in this regulation. These results add novel information on the immunomodulatory action of heat, in particular in the context of its possible use as an adjuvant therapeutic strategy to consider for the treatment of cancer
Distinct Roles for Human Cytomegalovirus Immediate Early Proteins IE1 and IE2 in the Transcriptional Regulation of MICA and PVR/CD155 Expression
No full textElimination of virus-infected cells by cytotoxic lymphocytes is triggered by activating receptors, among which NKG2D and DNAM-1/CD226 play an important role. Their ligands, that is, MHC class I-related chain (MIC) A/B and UL16-binding proteins (ULBP)1-6 (NKG2D ligand), Nectin-2/CD112, and poliovirus receptor (PVR)/CD155 (DNAM-1 ligand), are often induced on virus-infected cells, although some viruses, including human CMV (HCMV), can block their expression. In this study, we report that infection of different cell types with laboratory or low-passage HCMV strains upregulated MICA, ULBP3, and PVR, with NKG2D and DNAM-1 playing a role in NK cell-mediated lysis of infected cells. Inhibition of viral DNA replication with phosphonoformic acid did not prevent ligand upregulation, thus indicating that early phases of HCMV infection are involved in ligand increase. Indeed, the major immediate early (IE) proteins IE1 and IE2 stimulated the expression of MICA and PVR, but not ULBP3. IE2 directly activated MICA promoter via its binding to an IE2-responsive element that we identified within the promoter and that is conserved among different alleles of MICA. Both IE proteins were instead required for PVR upregulation via a mechanism independent of IE DNA binding activity. Finally, inhibiting IE protein expression during HCMV infection confirmed their involvement in ligand increase. We also investigated the contribution of the DNA damage response, a pathway activated by HCMV and implicated in ligand regulation. However, silencing of ataxia telangiectasia mutated, ataxia telangiectasia and Rad3-related protein, and DNA-dependent protein kinase did not influence ligand expression. Overall, these data reveal that MICA and PVR are directly regulated by HCMV IE proteins, and this may be crucial for the onset of an early host antiviral response
Innate immune activating ligand SUMOylation affects tumor cell recognition by NK cells
No full textNatural Killer cells are innate lymphocytes involved in tumor immunosurveillance. They express activating receptors able to recognize self-molecules poorly expressed on healthy cells but up-regulated upon stress conditions, including transformation. Regulation of ligand expression in tumor cells mainly relays on transcriptional mechanisms, while the involvement of ubiquitin or ubiquitin-like modifiers remains largely unexplored. Here, we focused on the SUMO pathway and demonstrated that the ligand of DNAM1 activating receptor, PVR, undergoes SUMOylation in multiple myeloma. Concurrently, we found that PVR is preferentially located in intracellular compartments in human multiple myeloma cell lines and malignant plasma cells and that inhibition of the SUMO pathway promotes its translocation to the cell surface, increasing tumor cell susceptibility to NK cell-mediated cytolysis. Our findings provide the first evidence of an innate immune activating ligand regulated by SUMOylation, and confer to this modification a novel role in impairing recognition and killing of tumor cells.Natural Killer cells are innate lymphocytes involved in tumor immunosurveillance. They express activating receptors able to recognize self-molecules poorly expressed on healthy cells but up-regulated upon stress conditions, including transformation. Regulation of ligand expression in tumor cells mainly relays on transcriptional mechanisms, while the involvement of ubiquitin or ubiquitin-like modifiers remains largely unexplored. Here, we focused on the SUMO pathway and demonstrated that the ligand of DNAM1 activating receptor, PVR, undergoes SUMOylation in multiple myeloma. Concurrently, we found that PVR is preferentially located in intracellular compartments in human multiple myeloma cell lines and malignant plasma cells and that inhibition of the SUMO pathway promotes its translocation to the cell surface, increasing tumor cell susceptibility to NK cell-mediated cytolysis. Our findings provide the first evidence of an innate immune activating ligand regulated by SUMOylation, and confer to this modification a novel role in impairing recognition and killing of tumor cells
Genome sequence of Rhodobacter sphaeroides strain WS8N
No full textCopyright © 2011, American Society for MicrobiologyRhodobacter sphaeroides is a metabolically diverse photosynthetic alphaproteobacterium found ubiquitously in soil and freshwater habitats. Here we present the annotated genome sequence of R. sphaeroides WS8N.This research was funded by the UK Biotechnology and Biological Sciences Research Council
Contrast media-induced nephropathy: how has Italy contributed in the past 30 years? A systematic review
No full textMaurizio Sessa,1,* Claudia Rossi,2,* Annamaria Mascolo,1 Cristina Scavone,1 Gabriella di Mauro,1 Roberto Grassi,2 Liberata Sportiello,1 Salvatore Cappabianca,2 Concetta Rafaniello1 1Section of Pharmacology “L Donatelli”, Department of Experimental Medicine, University of Campania “L Vanvitelli”, Naples, Italy; 2Section of Radiology and Radiotherapy, Department of Clinical and Experimental Medicine “Magrassi-Lanzara”, University of Campania “L Vanvitelli”, Naples, Italy *These authors contributed equally to this work Background and objective: The use of contrast media in Italy has exponentially increased in the past 3 decades. However, it is unknown whether there has been an increase in clinical research evaluating the risks associated with contrast media usage, especially regarding contrast-induced nephropathy. To fill this gap in knowledge, we performed a systematic review.Study eligibility criteria: Meta-analyses, observational studies, and clinical trials assessing contrast media-induced nephropathy as the safety outcome, in which at least one author was affiliated with an Italian university/health care structure, were eligble.Data sources: Ovid MEDLINE, Ovid Embase, Cochrane Methodology Register, and Web of Science were screened.Participants: Men and women exposed to contrast media.Results: In total, 60 original articles were retrieved with an incremental trend between 1990 and 2017. Cohort studies were the most common study design represented. In total, 45 of 60 (75.0%) studies were monocenter studies and 41 of 60 (68.3%) received no funding. In all, 91.7% of studies disclosed no conflicts of interest and 81.7% had no external collaboration. Most of the studies provided a level of evidence of III-2 (32/60; 53.3%) and II (23/60; 38.3%). In total, 50 of 60 studies (83.3%) were published in a scientific journal ranked in the first quartile of their subject area.Conclusion: There was an increased number of studies evaluating contrast-induced nephropathy in Italy during the last three decades. These studies covered procedures to prevent contrast-induced nephropathy or aimed to identify risk factors, biomarkers, and scores, and their related prognosis. Keywords: nephropathy, contrast media, Italy, systematic review, drug safety, adverse drug reaction, pharmacovigilance, post-marketing surveillanc
Functional Characterization of Promoter Variants of the Adiponectin Gene Complemented by Epidemiological Data
No full text# These authors contributed equally to the work. *Corresponding author
Corrigendum to “A cross-sectional study on the association between executive functions and social disabilities in people with a psychotic disorder” [Schizophr. Res. Cogn. Volume 40 (2025), article number: 100349]
No full textThe authors regret <not stating clearly that B.C. van Aken & R. Rietveld contributed equally to the manuscript. We would like to add a corrigendum where it states that the first and second author (B.C. van Aken & R. Rietveld) contributed equally>. The authors would like to apologise for any inconvenience caused.</p
Author Correction: A fast radio burst source at a complex magnetized site in a barred galaxy (Nature, (2022), 609, 7928, (685-688), 10.1038/s41586-022-05071-8)
No full textIn the version of this article initially published, an equal-contributor footnote was missing for authors H. Xu, J. R. Niu and P. Chen. The Author contributions section has been amended to read “H.X., J.R.N. and P.C. contributed equally and led the data analysis”. The changes have been made to the HTML and PDF versions of the article.link_to_subscribed_fulltex
Correction to “Ultrafast Cation Exchange in Supra-Quantum Dots through Nanoporous Internal Structure”
No full textThe author list should be “Hyunmi Doh, Juwon Park, Junhwa Lee, Jiwon Bang, Sanghwa Jeong, Wonseok Lee, Ho Jin, and Sungjee Kim”, with an addition of a co-author, Junhwa Lee. Hyunmi Doh, Juwon Park, and Junhwa Lee contributed equally to this work. This change was agreed to by all authors and is reflected in the authorship of this correction.11Nsciescopu
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