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Cancer Immunology, Immunotherapy : CII Nov 2023T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) expression has been a trending topic in recent years due to its differential expression in a wide... (Review)
Review
T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) expression has been a trending topic in recent years due to its differential expression in a wide range of neoplasms. TIM-3 is one of the key immune checkpoint receptors that interact with GAL-9, PtdSer, HMGB1 and CEACAM1. Initially identified on the surface of T helper 1 (Th1) lymphocytes and later on cytotoxic lymphocytes (CTLs), monocytes, macrophages, natural killer cells (NKs), and dendritic cells (DCs), TIM-3 plays a key role in immunoregulation. Recently, a growing body of evidence has shown that its differential expression in various tumor types indicates a specific prognosis for cancer patients. Here, we discuss which types of cancer TIM-3 can serve as a prognostic factor and the influence of coexpressed immune checkpoint inhibitors, such as LAG-3, PD-1, and CTLA-4 on patients' outcomes. Currently, experimental medicine involving TIM-3 has significantly enhanced the anti-tumor effect and improved patient survival. In this work, we summarized clinical trials incorporating TIM-3 targeting monoclonal and bispecific antibodies in monotherapy and combination therapy and highlighted the emerging role of cell-based therapies.
Topics: Humans; Antineoplastic Agents; Hepatitis A Virus Cellular Receptor 2; Immunity; Immunotherapy; Neoplasms
PubMed: 37567938
DOI: 10.1007/s00262-023-03516-1 -
Immunity Sep 2023Arginase 1 (Arg1), the enzyme catalyzing the conversion of arginine to ornithine, is a hallmark of IL-10-producing immunoregulatory M2 macrophages. However, its...
Arginase 1 (Arg1), the enzyme catalyzing the conversion of arginine to ornithine, is a hallmark of IL-10-producing immunoregulatory M2 macrophages. However, its expression in T cells is disputed. Here, we demonstrate that induction of Arg1 expression is a key feature of lung CD4 T cells during mouse in vivo influenza infection. Conditional ablation of Arg1 in CD4 T cells accelerated both virus-specific T helper 1 (Th1) effector responses and its resolution, resulting in efficient viral clearance and reduced lung pathology. Using unbiased transcriptomics and metabolomics, we found that Arg1-deficiency was distinct from Arg2-deficiency and caused altered glutamine metabolism. Rebalancing this perturbed glutamine flux normalized the cellular Th1 response. CD4 T cells from rare ARG1-deficient patients or CRISPR-Cas9-mediated ARG1-deletion in healthy donor cells phenocopied the murine cellular phenotype. Collectively, CD4 T cell-intrinsic Arg1 functions as an unexpected rheostat regulating the kinetics of the mammalian Th1 lifecycle with implications for Th1-associated tissue pathologies.
Topics: Animals; Humans; Mice; Arginase; CD4-Positive T-Lymphocytes; Glutamine; Influenza, Human; Kinetics; Lung; Mammals
PubMed: 37572656
DOI: 10.1016/j.immuni.2023.07.014 -
Allergologie Select 2023Although used for over 100 years, allergen immunotherapy (AIT) is still an indispensable tool in modern allergy managemen20t due to its potential to cure allergic... (Review)
Review
Although used for over 100 years, allergen immunotherapy (AIT) is still an indispensable tool in modern allergy managemen20t due to its potential to cure allergic diseases. Its current rapid development through the application of personalized and precision medicine approaches is strongly supported by advances in mHealth, component-resolved diagnosis (CRD)-based diagnostics, validation of novel biomarkers, advanced data management, and development of novel preparations. This review summarizes the key advances in the field and shows the perspectives for further development of next-generation AIT treatments.
PubMed: 38143940
DOI: 10.5414/ALX02379E -
Pathologie (Heidelberg, Germany) Dec 2023In this review focus article, we highlight the main modifications introduced in the latest 2022 International Consensus Classification and World Health Organization... (Review)
Review
In this review focus article, we highlight the main modifications introduced in the latest 2022 International Consensus Classification and World Health Organization classification (ICC and WHO-HAEM5) of mature T (and NK) cell neoplasms (PTCLs) and consequent implications for diagnostic practice. The changes result from recent advances in the genomic and molecular characterization of PTCLs and enhanced understanding of their pathobiology. Specifically, consideration is given to the following groups of diseases: Epstein-Barr virus (EBV)-associated neoplasms; follicular helper T cell lymphoma; anaplastic large cell lymphomas; primary intestinal T and NK cell lymphomas and lymphoproliferative disorders; and PTCL, not otherwise specified.
Topics: Humans; Lymphoma, T-Cell, Peripheral; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Killer Cells, Natural; Lymphoma, Large-Cell, Anaplastic
PubMed: 38047948
DOI: 10.1007/s00292-023-01260-y -
Viruses Aug 2023Hepatitis D virus (HDV) is a defective RNA virus with a negative-strand RNA genome encompassing less than 1700 nucleotides. The HDV genome encodes only for one protein,... (Review)
Review
Hepatitis D virus (HDV) is a defective RNA virus with a negative-strand RNA genome encompassing less than 1700 nucleotides. The HDV genome encodes only for one protein, the hepatitis delta antigen (HDAg), which exists in two forms acting as nucleoproteins. HDV depends on the envelope proteins of the hepatitis B virus as a helper virus for packaging its ribonucleoprotein complex (RNP). HDV is considered the causative agent for the most severe form of viral hepatitis leading to liver fibrosis/cirrhosis and hepatocellular carcinoma. Many steps of the life cycle of HDV are still enigmatic. This review gives an overview of the complete life cycle of HDV and identifies gaps in knowledge. The focus is on the description of cellular factors being involved in the life cycle of HDV and the deregulation of cellular pathways by HDV with respect to their relevance for viral replication, morphogenesis and HDV-associated pathogenesis. Moreover, recent progress in antiviral strategies targeting cellular structures is summarized in this article.
Topics: Animals; Hepatitis Delta Virus; Hepatitis delta Antigens; Antiviral Agents; Life Cycle Stages; Liver Cirrhosis; Liver Neoplasms
PubMed: 37632029
DOI: 10.3390/v15081687 -
ELife Jul 2023The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent of a major global outbreak of respiratory tract disease known as Coronavirus Disease 2019...
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent of a major global outbreak of respiratory tract disease known as Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 infects mainly lungs and may cause several immune-related complications, such as lymphocytopenia and cytokine storm, which are associated with the severity of the disease and predict mortality. The mechanism by which SARS-CoV-2 infection may result in immune system dysfunction is still not fully understood. Here, we show that SARS-CoV-2 infects human CD4 T helper cells, but not CD8 T cells, and is present in blood and bronchoalveolar lavage T helper cells of severe COVID-19 patients. We demonstrated that SARS-CoV-2 spike glycoprotein (S) directly binds to the CD4 molecule, which in turn mediates the entry of SARS- CoV-2 in T helper cells. This leads to impaired CD4 T cell function and may cause cell death. SARS-CoV-2-infected T helper cells express higher levels of IL-10, which is associated with viral persistence and disease severity. Thus, CD4-mediated SARS-CoV-2 infection of T helper cells may contribute to a poor immune response in COVID-19 patients.
Topics: Humans; SARS-CoV-2; COVID-19; CD8-Positive T-Lymphocytes; T-Lymphocytes, Helper-Inducer; Lung
PubMed: 37523305
DOI: 10.7554/eLife.84790 -
Clinical Reviews in Allergy & Immunology Aug 2023X-linked agammaglobulinaemia (XLA) is a primary immunodeficiency (PID) resulting from a defect in the B cell development. It has conventionally been thought that T cells... (Review)
Review
X-linked agammaglobulinaemia (XLA) is a primary immunodeficiency (PID) resulting from a defect in the B cell development. It has conventionally been thought that T cells play a major role in the development and function of the B cell compartment. However, it has also been shown that B cells and T cells undergo bidirectional interactions and B cells also influence the structure and function of the T cell compartment. Patients with XLA offer a unique opportunity to understand the effect of absent B cells on the T cell compartment. In this review, we provide an update on abnormalities in the T cell compartment in patients with XLA. Studies have shown impaired memory T cells, follicular helper T cells, T regulatory cells and T helper 17 in patients with XLA. In addition, these patients have also been reported to have abnormal delayed cell-mediated immune responses and vaccine-specific T cell-mediated immune responses; defective T helper cell polarization and impaired T cell receptor diversity. At present, the clinical significance of these T cell abnormalities has not been studied in detail. However, these abnormalities may result in an increased risk of viral infections, autoimmunity, autoinflammation and possibly chronic lung disease. Abnormal response to SARS-Cov2 vaccine in patients with XLA and prolonged persistence of SARS-Cov2 virus in the respiratory tract of these patients may be related to abnormalities in the T cell compartment.
Topics: Humans; Agammaglobulinaemia Tyrosine Kinase; RNA, Viral; COVID-19; SARS-CoV-2; Mutation
PubMed: 35708830
DOI: 10.1007/s12016-022-08949-7 -
Frontiers in Cellular and Infection... 2023Hepatitis is an inflammation of the liver whose etiology is very heterogeneous. The most common cause of hepatitis is viral infections from hepatotropic viruses,... (Review)
Review
Hepatitis is an inflammation of the liver whose etiology is very heterogeneous. The most common cause of hepatitis is viral infections from hepatotropic viruses, including hepatitis A, B, C, D and E. However, other factors such as infections from other agents, metabolic disorders, or autoimmune reactions can also contribute to hepatitis, albeit to a lesser extent. On April 5, 2022, the United Kingdom Health Security Agency alerted the World Health Organization (WHO) on the increased incidence of severe acute hepatitis of unknown causes (not A-E) in previously healthy young children, with symptoms of liver failure that in some cases required liver transplantation. By July 2022, 1,296 cases were reported in 37 countries. Acute hepatitis of unknown causes is not an exceptional phenomenon: in fact, it represents more than 30% of cases of acute hepatitis in children, however in the present instance the large proportion of severe cases was surprising and alarming (6% of liver transplants and almost 3% mortality). Multiple hypotheses have been proposed to explain the etiology of such higher proportion of acute hepatitis, including their co-occurrence in the context of COVID-19 pandemic. This is a review of the history of a clinical threat that has put in check a world health care system highly sensitized by the current COVID-19 pandemics, and that it looks like has ended with the arguments that the severe acute pediatric hepatitis is caused by Adeno-associated virus 2 (AAV2) infection associated with a coinfection with a helper virus (human Adenovirus HAdV or human herpesvirus 6) in susceptible children carrying HLA-class II antigen HLA-DRB1*04:01.
Topics: Humans; Child; Child, Preschool; Pandemics; COVID-19; Liver Transplantation; Acute Disease; Hepatitis
PubMed: 37808908
DOI: 10.3389/fcimb.2023.1175996 -
Cancers Jun 2023Epstein-Barr virus (EBV) is a ubiquitous herpes virus associated with various cancers. EBV establishes latency with life-long persistence in memory B-cells and can...
Epstein-Barr virus (EBV) is a ubiquitous herpes virus associated with various cancers. EBV establishes latency with life-long persistence in memory B-cells and can reactivate lytic infection placing immunocompromised individuals at risk for EBV-driven lymphoproliferative disorders (EBV-LPD). Despite the ubiquity of EBV, only a small percentage of immunocompromised patients (~20%) develop EBV-LPD. Engraftment of immunodeficient mice with peripheral blood mononuclear cells (PBMCs) from healthy EBV-seropositive donors leads to spontaneous, malignant, human B-cell EBV-LPD. Only about 20% of EBV+ donors induce EBV-LPD in 100% of engrafted mice (High-Incidence, HI), while another 20% of donors never generate EBV-LPD (No-Incidence, NI). Here, we report HI donors to have significantly higher basal T follicular helper (Tfh) and regulatory T-cells (Treg), and depletion of these subsets prevents/delays EBV-LPD. Transcriptomic analysis of CD4+ T cells from ex vivo HI donor PBMC revealed amplified cytokine and inflammatory gene signatures. HI vs. NI donors showed a marked reduction in IFNγ production to EBV latent and lytic antigen stimulation. In addition, we observed abundant myeloid-derived suppressor cells in HI donor PBMC that decreased CTL proliferation in co-cultures with autologous EBV+ lymphoblasts. Our findings identify potential biomarkers that may identify individuals at risk for EBV-LPD and suggest possible strategies for prevention.
PubMed: 37297008
DOI: 10.3390/cancers15113046