scholarly journals Long‐term peripheral immune cell profiling reveals further targets of oral cladribine in MS

2020 ◽  
Vol 7 (11) ◽  
pp. 2199-2212 ◽  
Author(s):  
Tobias Moser ◽  
Kerstin Schwenker ◽  
Michael Seiberl ◽  
Julia Feige ◽  
Katja Akgün ◽  
...  
Keyword(s):  
Immune Cell ◽  
Peripheral Immune Cell

Identification of WDFY3 Neoantigens as Prognostic Markers in Longterm Survivors of Extrahepatic Cholangiocarcinoma

2020 ◽  
Vol 20 (11) ◽  
pp. 875-886
Author(s):  
Yingyi Wang ◽  
Bao Jin ◽  
Na Zhou ◽  
Zhao Sun ◽  
Jiayi Li ◽  
...  
Keyword(s):  
Antitumor Immunity ◽  
Prognostic Markers ◽  
Immune Cell ◽  
Neutrophil Infiltration ◽  
Computational Biophysics ◽  
Extrahepatic Cholangiocarcinoma ◽  
Whole Exome ◽  
Mutation Burden ◽  
Long Term Survivors

Background:: Neoantigens are newly formed antigens that have not been previously recognized by the immune system. They may arise from altered tumor proteins that form as a result of mutations. Although neoantigens have recently been linked to antitumor immunity in long-term survivors of cancers, such as melanoma and colorectal cancer, their prognostic and immune-modulatory role in many cancer types remains undefined. Objective: The purpose of this study is to identify prognostic markers for long-term extrahepatic cholangiocarcinoma (EHCC) survival. Methods: We investigated neoantigens in EHCC, a rare, aggressive cancer with a 5-year overall survival rate lower than 10%, using a combination of whole-exome sequencing (WES), RNA sequencing (RNA-seq), computational biophysics, and immunohistochemistry. Results: : Our analysis revealed a decreased neutrophil infiltration-related trend of high-quality neoantigen load with IC50 <500 nM (r=-0.445, P=0.043). Among 24 EHCC patients examined, we identified four long-term survivors with WDFY3 neoantigens and none with WDFY3 neoantigens in the short-term survivors. The WDFY3 neoantigens are associated with a lower infiltration of neutrophils (p=0.013), lower expression of CCL5 (p=0.025), CXCL9 (p=0.036) and TIGIT (p=0.016), and less favorable prognosis (p=0.030). In contrast, the prognosis was not significantly associated with tumor mutation burden, neoantigen load, or immune cell infiltration. Conclusion:: We suggest that the WDFY3 neoantigens may affect prognosis by regulating antitumor immunity and that the WDFY3 neoantigens may be harnessed as potential targets for immunotherapy of EHCC.

scholarly journals Genotype of Immunologically Hot or Cold Tumors Determines the Antitumor Immune Response and Efficacy by Fully Virulent Retargeted oHSV

Viruses ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1747
Author(s):  
Tatiana Gianni ◽  
Valerio Leoni ◽  
Mara Sanapo ◽  
Federico Parenti ◽  
Daniela Bressanin ◽  
...  
Keyword(s):  
Immune Cell ◽  
Immune Protection ◽  
T Regulatory Cell ◽  
Immune Markers ◽  
Innate Response ◽  
Cell Content ◽  
Immune Profiling ◽  
Insight Into

We report on the efficacy of the non-attenuated HER2-retargeted oHSV named R-337 against the immunologically hot CT26-HER2 tumor, and an insight into the basis of the immune protection. Preliminarily, we conducted an RNA immune profiling and immune cell content characterization of CT26-HER2 tumor in comparison to the immunologically cold LLC1-HER2 tumor. CT26-HER2 tumor was implanted into HER2-transgenic BALB/c mice. Hallmarks of R-337 effects were the protection from primary tumor, long-term adaptive vaccination directed to both HER2 and CT26-wt cell neoantigens. The latter effect differentiated R-337 from OncoVEXGM-CSF. As to the basis of the immune protection, R-337 orchestrated several changes to the tumor immune profile, which cumulatively reversed the immunosuppression typical of this tumor (graphical abstract). Thus, Ido1 (inhibitor of T cell anticancer immunity) levels and T regulatory cell infiltration were decreased; Cd40 and Cd27 co-immunostimulatory markers were increased; the IFNγ cascade was activated. Of note was the dampening of IFN-I response, which we attribute to the fact that R-337 is fully equipped with genes that contrast the host innate response. The IFN-I shut-down likely favored viral replication and the expression of the mIL-12 payload, which, in turn, boosted the antitumor response. The results call for a characterization of tumor immune markers to employ oncolytic herpesviruses more precisely.

scholarly journals Neuroinflammation and Its Impact on the Pathogenesis of COVID-19

2021 ◽  
Vol 8 ◽  
Author(s):  
Mohammed M. Almutairi ◽  
Farzane Sivandzade ◽  
Thamer H. Albekairi ◽  
Faleh Alqahtani ◽  
Luca Cucullo
Keyword(s):  
Immune System ◽  
Molecular Mechanisms ◽  
Potential Role ◽  
Immune Cell ◽  
Clinical Manifestations ◽  
Cell Infiltration ◽  
Cellular Mechanisms ◽  
Cytokine Levels

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The clinical manifestations of COVID-19 include dry cough, difficult breathing, fever, fatigue, and may lead to pneumonia and respiratory failure. There are significant gaps in the current understanding of whether SARS-CoV-2 attacks the CNS directly or through activation of the peripheral immune system and immune cell infiltration. Although the modality of neurological impairments associated with COVID-19 has not been thoroughly investigated, the latest studies have observed that SARS-CoV-2 induces neuroinflammation and may have severe long-term consequences. Here we review the literature on possible cellular and molecular mechanisms of SARS-CoV-2 induced-neuroinflammation. Activation of the innate immune system is associated with increased cytokine levels, chemokines, and free radicals in the SARS-CoV-2-induced pathogenic response at the blood-brain barrier (BBB). BBB disruption allows immune/inflammatory cell infiltration into the CNS activating immune resident cells (such as microglia and astrocytes). This review highlights the molecular and cellular mechanisms involved in COVID-19-induced neuroinflammation, which may lead to neuronal death. A better understanding of these mechanisms will help gain substantial knowledge about the potential role of SARS-CoV-2 in neurological changes and plan possible therapeutic intervention strategies.

scholarly journals The Causes and Long-Term Consequences of Viral Encephalitis

2021 ◽  
Vol 15 ◽  
Author(s):  
Karen Bohmwald ◽  
Catalina A. Andrade ◽  
Nicolás M. S. Gálvez ◽  
Valentina P. Mora ◽  
José T. Muñoz ◽  
...  
Keyword(s):  
Viral Encephalitis ◽  
Viral Infections ◽  
Immune Cell ◽  
Clinical Symptoms ◽  
Brain Inflammation ◽  
High Morbidity ◽  
Stiff Neck ◽  
The Impact ◽  
The Brain

Reports regarding brain inflammation, known as encephalitis, have shown an increasing frequency during the past years. Encephalitis is a relevant concern to public health due to its high morbidity and mortality. Infectious or autoimmune diseases are the most common cause of encephalitis. The clinical symptoms of this pathology can vary depending on the brain zone affected, with mild ones such as fever, headache, confusion, and stiff neck, or severe ones, such as seizures, weakness, hallucinations, and coma, among others. Encephalitis can affect individuals of all ages, but it is frequently observed in pediatric and elderly populations, and the most common causes are viral infections. Several viral agents have been described to induce encephalitis, such as arboviruses, rhabdoviruses, enteroviruses, herpesviruses, retroviruses, orthomyxoviruses, orthopneumovirus, and coronaviruses, among others. Once a neurotropic virus reaches the brain parenchyma, the resident cells such as neurons, astrocytes, and microglia, can be infected, promoting the secretion of pro-inflammatory molecules and the subsequent immune cell infiltration that leads to brain damage. After resolving the viral infection, the local immune response can remain active, contributing to long-term neuropsychiatric disorders, neurocognitive impairment, and degenerative diseases. In this article, we will discuss how viruses can reach the brain, the impact of viral encephalitis on brain function, and we will focus especially on the neurocognitive sequelae reported even after viral clearance.

scholarly journals Targeting the Blood-Brain Barrier to Prevent Sepsis-Associated Cognitive Impairment

2019 ◽  
Vol 11 ◽  
pp. 117957351984065 ◽  
Author(s):  
Divine C Nwafor ◽  
Allison L Brichacek ◽  
Afroz S Mohammad ◽  
Jessica Griffith ◽  
Brandon P Lucke-Wold ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Blood Brain Barrier ◽  
Immune Cell ◽  
The United States ◽  
Brain Barrier ◽  
Blood Brain ◽  
Systemic Inflammatory Disease ◽  
Sepsis Survivors ◽  
The Brain

Sepsis is a systemic inflammatory disease resulting from an infection. This disorder affects 750 000 people annually in the United States and has a 62% rehospitalization rate. Septic symptoms range from typical flu-like symptoms (eg, headache, fever) to a multifactorial syndrome known as sepsis-associated encephalopathy (SAE). Patients with SAE exhibit an acute altered mental status and often have higher mortality and morbidity. In addition, many sepsis survivors are also burdened with long-term cognitive impairment. The mechanisms through which sepsis initiates SAE and promotes long-term cognitive impairment in septic survivors are poorly understood. Due to its unique role as an interface between the brain and the periphery, numerous studies support a regulatory role for the blood-brain barrier (BBB) in the progression of acute and chronic brain dysfunction. In this review, we discuss the current body of literature which supports the BBB as a nexus which integrates signals from the brain and the periphery in sepsis. We highlight key insights on the mechanisms that contribute to the BBB’s role in sepsis which include neuroinflammation, increased barrier permeability, immune cell infiltration, mitochondrial dysfunction, and a potential barrier role for tissue non-specific alkaline phosphatase (TNAP). Finally, we address current drug treatments (eg, antimicrobials and intravenous immunoglobulins) for sepsis and their potential outcomes on brain function. A comprehensive understanding of these mechanisms may enable clinicians to target specific aspects of BBB function as a therapeutic tool to limit long-term cognitive impairment in sepsis survivors.

scholarly journals Long-Term Effects of Experimental Human Endotoxemia on Immune Cell Function

Shock ◽  
2019 ◽  
Vol 51 (6) ◽  
pp. 678-689 ◽  
Author(s):  
Yessica Alina Rodriguez-Rosales ◽  
Matthijs Kox ◽  
Esther van Rijssen ◽  
Bram van Cranenbroek ◽  
Marina van Welie ◽  
...  
Keyword(s):  
Cell Function ◽  
Immune Cell ◽  
Immune Cell Function ◽  
Long Term Effects ◽  
Human Endotoxemia

scholarly journals Characterization of Peripheral Immune Cell Subsets in Patients with Acute and Chronic Cerebrovascular Disease: A Case-Control Study

2015 ◽  
Vol 16 (10) ◽  
pp. 25433-25449 ◽  
Author(s):  
Peter Kraft ◽  
Christiane Drechsler ◽  
Michael Schuhmann ◽  
Ignaz Gunreben ◽  
Christoph Kleinschnitz
Keyword(s):  
Cerebrovascular Disease ◽  
Case Control Study ◽  
Immune Cell ◽  
Case Control ◽  
Immune Cell Subsets ◽  
Peripheral Immune Cell ◽  
Control Study
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