Search results for "Nod"

Enhancement of Antigen Presentation by Deletion of Viral Immune Evasion Genes Prevents Lethal Cytomegalovirus Disease in Minor Histocompatibility Ant…

2020

Hematoablative treatment followed by hematopoietic cell transplantation (HCT) for reconstituting the co-ablated immune system is a therapeutic option to cure aggressive forms of hematopoietic malignancies. In cases of family donors or unrelated donors, immunogenetic mismatches in major histocompatibility complex (MHC) and/or minor histocompatibility (minor-H) loci are unavoidable and bear a risk of graft-vs.-host reaction and disease (GvHR/D). Transient immunodeficiency inherent to the HCT protocol favors a productive reactivation of latent cytomegalovirus (CMV) that can result in multiple-organ CMV disease. In addition, there exists evidence from a mouse model of MHC class-I-mismatched GvH…

Insufficient Antigen Presentation Due to Viral Immune Evasion Explains Lethal Cytomegalovirus Organ Disease After Allogeneic Hematopoietic Cell Trans…

2020

Reactivation of latent cytomegalovirus (CMV) poses a clinical problem in transiently immunocompromised recipients of hematopoietic cell (HC) transplantation (HCT) by viral histopathology that results in multiple organ manifestations. Compared to autologous HCT and to syngeneic HCT performed with identical twins as HC donor and recipient, lethal outcome of CMV infection is more frequent in allogeneic HCT with MHC/HLA or minor histocompatibility loci mismatch between donor and recipient. It is an open question if a graft-versus-host (GvH) reaction exacerbates CMV disease, or if CMV exacerbates GvH disease (GvHD), or if interference is mutual. Here we have used a mouse model of experimental HC…

Psammomatoid Calcification-Rich Oncocytic Thyroid Adenoma With Clear-Cell Change

2018

Abundant calcifications and clear-cell change may occur in oncocytic thyroid adenoma (OTA). We aimed to report the features of a case of OTA peculiar by the presence of extensive calcifications and of a clear-cell component. The OTA was detected on a right thyroid lobectomy specimen. Clear-cell change was observed in 15%-20% of the cells. Numerous, focally confluent psammomatoid calcifications, resulting in macrocalcifications, were identified. The nodule cells, uni- or multinucleated oncocytes, including those with clear cytoplasm, expressed heterogeneously TTF1, S100 protein, Bcl2, CD10, as well as CD138 and CD56. Lipid-droplet markers adipophilin and TIP47 were also expressed. In conclus…

Human molecular chaperones share with SARS-CoV-2 antigenic epitopes potentially capable of eliciting autoimmunity against endothelial cells: possible…

2020

Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), the cause of COVID-19 disease, has the potential to elicit autoimmunity because mimicry of human molecular chaperones by viral proteins. We compared viral proteins with human molecular chaperones, many of which are heat shock proteins, to determine if they share amino acid-sequence segments with immunogenic-antigenic potential, which can elicit cross-reactive antibodies and effector immune cells with the capacity to damage-destroy human cells by a mechanism of autoimmunity. We identified the chaperones that can putatively participate in molecular mimicry phenomena after SARS-CoV-2 infection, focusing on those for which endotheli…

2016

AbstractThe different factors involved in the growth process of complex networks imprint valuable information in their observable topologies. How to exploit this information to accurately predict structural network changes is the subject of active research. A recent model of network growth sustains that the emergence of properties common to most complex systems is the result of certain trade-offs between node birth-time and similarity. This model has a geometric interpretation in hyperbolic space, where distances between nodes abstract this optimisation process. Current methods for network hyperbolic embedding search for node coordinates that maximise the likelihood that the network was pro…

Centrality in Complex Networks with Overlapping Community Structure

2019

AbstractIdentifying influential spreaders in networks is an essential issue in order to prevent epidemic spreading, or to accelerate information diffusion. Several centrality measures take advantage of various network topological properties to quantify the notion of influence. However, the vast majority of works ignore its community structure while it is one of the main features of many real-world networks. In a recent study, we show that the centrality of a node in a network with non-overlapping communities depends on two features: Its local influence on the nodes belonging to its community, and its global influence on the nodes belonging to the other communities. Using global and local co…

Peptide Processing Is Critical for T-Cell Memory Inflation and May Be Optimized to Improve Immune Protection by CMV-Based Vaccine Vectors.

2016

Cytomegalovirus (CMV) elicits long-term T-cell immunity of unparalleled strength, which has allowed the development of highly protective CMV-based vaccine vectors. Counterintuitively, experimental vaccines encoding a single MHC-I restricted epitope offered better immune protection than those expressing entire proteins, including the same epitope. To clarify this conundrum, we generated recombinant murine CMVs (MCMVs) encoding well-characterized MHC-I epitopes at different positions within viral genes and observed strong immune responses and protection against viruses and tumor growth when the epitopes were expressed at the protein C-terminus. We used the M45-encoded conventional epitope HGI…

ASO Author Reflections: How Long will We Perform Lymphadenectomy in Endometrial Cancer Patients?

2022

Abstract Objectives To compare survival and progression outcomes between 2 nodal assessment approaches in patients with nonbulky stage IIIC endometrial cancer (EC). Methods Patients with stage IIIC EC treated at 2 institutions were retrospectively identified. At 1 institution, a historical series (2004–2008) was treated with systematic pelvic and para-aortic lymphadenectomy (LND cohort). At the other institution, more contemporary patients (2006–2013) were treated using a sentinel lymph node algorithm (SLN cohort). Outcomes (hazard ratios [HRs]) within the first 5 years after surgery were compared between cohorts using Cox models adjusted for type of adjuvant therapy. Results The study incl…

NOD-like receptors: major players (and targets) in the interface between innate immunity and cancer

2019

Innate immunity comprises several inflammation-related modulatory pathways which receive signals from an array of membrane-bound and cytoplasmic pattern recognition receptors (PRRs). The NLRs (NACHT (NAIP (neuronal apoptosis inhibitor protein), C2TA (MHC class 2 transcription activator), HET-E (incompatibility locus protein from Podospora anserina) and TP1 (telomerase-associated protein) and Leucine-Rich Repeat (LRR) domain containing proteins) relate to a large family of cytosolic innate receptors, involved in detection of intracellular pathogens and endogenous byproducts of tissue injury. These receptors may recognize pathogen-associated molecular patterns (PAMPs) and/or danger-associated…

Assessment of intratumor immune-microenvironment in colorectal cancers with extranodal extension of nodal metastases

2018

Background: No data is available on the molecular background of the extra-nodal extension (ENE) of lymph node metastasis (LN) in colorectal cancer (CRC). Methods: A series of 22 ENE-positive CRCs was considered and three samples per case were selected (the primary CRC, an ENE-negative and an ENE-positive metastatic LN). Samples (n=66) were analysed by immunohistochemistry for PD-L1, CD4, CD8, CD68 and CD80. Fifteen out of twenty-two cases were further profiled through a hotspot multigene mutational custom panel, including 164 hotspot regions of AKT1, APC, BRAF, CTNNB1, KIT, KRAS, NRAS, PDGFRA, PIK3CA, PTEN and TP53 genes. Results: A significantly higher percentage of CD4-, CD8- and CD68-pos…