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Biomedicines
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State-of-the-Art Immunology and Immunotherapy in Europe
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State-of-the-Art Immunology and Immunotherapy in Europe

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Immunology and Immunotherapy".

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 18851

Special Issue Editor

Dr. Juan Gambini

E-Mail Website
Guest Editor
Freshage Research Group, Department of Physiology, Faculty of Medicine, University of Valencia, E46010 Valencia, Spain
Interests: diet; oxidative stress; longevity; aging; polyphenols
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Immunity represents one of the main pillars of longevity. The risk of suffering from diseases decreases in individuals with a more effective immune system. Why do individuals who reach 100 years of age have such powerful immunity? This depends innately on our genetics. Stress, vaccines, drugs, etc., will also positively or negatively influence our immune system and, therefore, our health. In this Special Issue, we plan to collect studies that describe the behavior of the immune system and explore how to modulate it so that it is our own body that cures us of diseases and allows us to live a healthier life in old age.

Prof. Dr. Juan Gambini
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • immunology
  • immunotherapy
  • lymphocytes
  • macrophages
  • eosinophils
  • neutrophils
  • diseases

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Related Special Issue

Published Papers (7 papers)

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Research

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13 pages, 2013 KiB  
Article
Investigating Acute Hepatitis after SARS-CoV-2 Vaccination or Infection: A Genetic Case Series
by Elisa Bernasconi, Matteo Biagi, Stefania Di Agostino, Carmela Cursaro, Cristina Felicani, Enrico Ronconi, Elena Franchi, Arianna Carmen Costanzo, Filippo Gabrielli, Alessia Cavicchioli, Giuseppe Ienopoli, Paolo Marenghi, Alessandra Bartoli, Beatrice Serra, Davide Scalabrini, Pamela Sighinolfi and Pietro Andreone
Biomedicines 2023, 11(10), 2848; https://doi.org/10.3390/biomedicines11102848 - 20 Oct 2023
Cited by 2 | Viewed by 1830
Abstract
(1) Background: Despite the advantages of COVID-19 vaccination, rare cases of acute hepatitis developing after the administration of the COVID-19 vaccine or the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been reported. The aim of the study is to describe a [...] Read more.
(1) Background: Despite the advantages of COVID-19 vaccination, rare cases of acute hepatitis developing after the administration of the COVID-19 vaccine or the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been reported. The aim of the study is to describe a case series of patients who experienced the onset of acute hepatitis, with or without autoimmune features, following SARS-CoV-2 vaccination or infection and to hypothesize a genetic susceptibility in the pathogenesis. (2) Methods: A group of patients with acute onset hepatitis following SARS-CoV-2 vaccination or infection were evaluated in our hepatology outpatient clinic, where they underwent biochemical and autoimmune tests. Hepatitis A (HAV), B (HBV), and C virus (HCV), cytomegalovirus (CMV), Epstein–Barr virus (EBV), and human immunodeficiency virus (HIV) infections were excluded. Patients with a diagnosis of autoimmune hepatitis (AIH) or drug-induced liver injury (DILI) underwent HLA typing and histological testing. (3) Results: Five patients experienced new-onset AIH after COVID-19 vaccination, one of which developed mild symptoms after vaccination that strongly worsened during subsequent SARS-CoV-2 infection. One patient had AIH relapse after COVID-19 vaccination while on maintenance immunosuppressive treatment. All of them had HLA DRB1 alleles known to confer susceptibility to AIH (HLA DRB1*03,*07,*13,*14), and in three of them, HLA DRB1*11 was also detected. Two patients developed acute hepatitis without autoimmune hallmarks which resolved spontaneously, both positive for HLA DRB1*11. (4) Conclusions: An association between AIH and COVID-19 vaccine or infection can be hypothesized in individuals with a genetic predisposition. In patients without autoimmune features and spontaneous improvement of hypertransaminasemia, the diagnosis of drug-induced liver injury (DILI) is probable. Further studies are needed to determine the presence of an actual association and identify a possible role of HLA DRB1*11 in the pathogenesis of acute liver injury after SARS-CoV2 vaccination or infection. Full article
(This article belongs to the Special Issue State-of-the-Art Immunology and Immunotherapy in Europe)
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25 pages, 4970 KiB  
Article
Adenovirus-Inspired Virus-like-Particles Displaying Melanoma Tumor Antigen Specifically Target Human DC Subsets and Trigger Antigen-Specific Immune Responses
by Solène Besson, David Laurin, Cyrielle Chauvière, Michel Thépaut, Jean-Philippe Kleman, Mylène Pezet, Olivier Manches, Franck Fieschi, Caroline Aspord and Pascal Fender
Biomedicines 2022, 10(11), 2881; https://doi.org/10.3390/biomedicines10112881 - 10 Nov 2022
Cited by 1 | Viewed by 2226
Abstract
Virus-like particles constitute versatile vectors that can be used as vaccine platforms in many fields from infectiology and more recently to oncology. We previously designed non-infectious adenovirus-inspired 60-mer dodecahedric virus-like particles named ADDomers displaying on their surface either a short epitope or a [...] Read more.
Virus-like particles constitute versatile vectors that can be used as vaccine platforms in many fields from infectiology and more recently to oncology. We previously designed non-infectious adenovirus-inspired 60-mer dodecahedric virus-like particles named ADDomers displaying on their surface either a short epitope or a large tumor/viral antigen. In this work, we explored for the first time the immunogenicity of ADDomers exhibiting melanoma-derived tumor antigen/epitope and their impact on the features of human dendritic cell (DC) subsets. We first demonstrated that ADDomers displaying tumor epitope/antigen elicit a strong immune-stimulating potential of human DC subsets (cDC2s, cDC1s, pDCs), which were able to internalize and cross-present tumor antigen, and subsequently cross-prime antigen-specific T-cell responses. To further limit off-target effects and enhance DC targeting, we engineered specific motifs to de-target epithelial cells and improve DCs’ addressing. The improved engineered platform making it possible to display large antigen represents a tool to overcome the barrier of immune allele restriction, broadening the immune response, and paving the way to its potential utilization in humans as an off-the-shelf vaccine. Full article
(This article belongs to the Special Issue State-of-the-Art Immunology and Immunotherapy in Europe)
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20 pages, 1484 KiB  
Article
Immunomodulation by Hemoadsorption—Changes in Hepatic Biotransformation Capacity in Sepsis and Septic Shock: A Prospective Study
by Janina Praxenthaler, Elke Schwier, Simon Altmann, Carmen Kirchner, Julian Bialas, Dietrich Henzler and Thomas Köhler
Biomedicines 2022, 10(10), 2340; https://doi.org/10.3390/biomedicines10102340 - 20 Sep 2022
Cited by 2 | Viewed by 1864
Abstract
Background: Sepsis is often associated with liver dysfunction, which is an indicator of poor outcomes. Specific diagnostic tools that detect hepatic dysfunction in its early stages are scarce. So far, the immune modulatory effects of hemoadsorption with CytoSorb® on liver function are [...] Read more.
Background: Sepsis is often associated with liver dysfunction, which is an indicator of poor outcomes. Specific diagnostic tools that detect hepatic dysfunction in its early stages are scarce. So far, the immune modulatory effects of hemoadsorption with CytoSorb® on liver function are unclear. Method: We assessed the hepatic function by using the dynamic LiMAx® test and biochemical parameters in 21 patients with sepsis or septic shock receiving CytoSorb® in a prospective, observational study. Points of measurement: T1: diagnosis of sepsis or septic shock; T2 and T3: 24 h and 48 h after the start of CytoSorb®; T4: 24 h after termination of CytoSorb®. Results: The hepatic biotransformation capacity measured by LiMAx® was severely impaired in up to 95 % of patients. Despite a rapid shock reversal under CytoSorb®, a significant improvement in LiMAx® values appeared from T3 to T4. This decline and recovery of liver function were not reflected by common parameters of hepatic metabolism that remained mostly within the normal range. Conclusions: Hepatic dysfunction can effectively and safely be diagnosed with LiMAx® in ventilated ICU patients under CytoSorb®. Various static liver parameters are of limited use since they do not adequately reflect hepatic dysfunction and impaired hepatic metabolism. Full article
(This article belongs to the Special Issue State-of-the-Art Immunology and Immunotherapy in Europe)
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17 pages, 2035 KiB  
Article
Human iNKT Cells Modulate Macrophage Survival and Phenotype
by J. Pedro Loureiro, Mariana S. Cruz, Ana P. Cardoso, Maria J. Oliveira and M. Fátima Macedo
Biomedicines 2022, 10(7), 1723; https://doi.org/10.3390/biomedicines10071723 - 17 Jul 2022
Cited by 2 | Viewed by 2757
Abstract
CD1d-restricted invariant Natural Killer T (iNKT) cells are unconventional innate-like T cells whose functions highly depend on the interactions they establish with other immune cells. Although extensive studies have been reported on the communication between iNKT cells and macrophages in mice, less data [...] Read more.
CD1d-restricted invariant Natural Killer T (iNKT) cells are unconventional innate-like T cells whose functions highly depend on the interactions they establish with other immune cells. Although extensive studies have been reported on the communication between iNKT cells and macrophages in mice, less data is available regarding the relevance of this crosstalk in humans. Here, we dove into the human macrophage-iNKT cell axis by exploring how iNKT cells impact the survival and polarization of pro-inflammatory M1-like and anti-inflammatory M2-like monocyte-derived macrophages. By performing in vitro iNKT cell-macrophage co-cultures followed by flow cytometry analysis, we demonstrated that antigen-stimulated iNKT cells induce a generalized activated state on all macrophage subsets, leading to upregulation of CD40 and CD86 expression. CD40L blocking with a specific monoclonal antibody prior to co-cultures abrogated CD40 and CD86 upregulation, thus indicating that iNKT cells required CD40-CD40L co-stimulation to trigger macrophage activation. In addition, activated iNKT cells were cytotoxic towards macrophages in a CD1d-dependent manner, killing M1-like macrophages more efficiently than their naïve M0 or anti-inflammatory M2-like counterparts. Hence, this work highlighted the role of human iNKT cells as modulators of macrophage survival and phenotype, untangling key features of the human macrophage-iNKT cell axis and opening perspectives for future therapeutic modulation. Full article
(This article belongs to the Special Issue State-of-the-Art Immunology and Immunotherapy in Europe)
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16 pages, 2922 KiB  
Article
Resilience of Spike-Specific Immunity Induced by COVID-19 Vaccines against SARS-CoV-2 Variants
by Laura Ballesteros-Sanabria, Hector F. Pelaez-Prestel, Alvaro Ras-Carmona and Pedro A. Reche
Biomedicines 2022, 10(5), 996; https://doi.org/10.3390/biomedicines10050996 - 26 Apr 2022
Cited by 8 | Viewed by 2540
Abstract
The outbreak of SARS-CoV-2 leading to the declaration of the COVID-19 global pandemic has led to the urgent development and deployment of several COVID-19 vaccines. Many of these new vaccines, including those based on mRNA and adenoviruses, are aimed to generate neutralizing antibodies [...] Read more.
The outbreak of SARS-CoV-2 leading to the declaration of the COVID-19 global pandemic has led to the urgent development and deployment of several COVID-19 vaccines. Many of these new vaccines, including those based on mRNA and adenoviruses, are aimed to generate neutralizing antibodies against the spike glycoprotein, which is known to bind to the receptor angiotensin converting enzyme 2 (ACE2) in host cells via the receptor-binding domain (RBD). Antibodies binding to this domain can block the interaction with the receptor and prevent viral entry into the cells. Additionally, these vaccines can also induce spike-specific T cells which could contribute to providing protection against the virus. However, the emergence of new SARS-CoV-2 variants can impair the immunity generated by COVID-19 vaccines if mutations occur in cognate epitopes, precluding immune recognition. Here, we evaluated the chance of five SARS-CoV-2 variants of concern (VOCs), Alpha, Beta, Gamma, Delta and Omicron, to escape spike-specific immunity induced by vaccines. To that end, we examined the impact of the SARS-CoV-2 variant mutations on residues located on experimentally verified spike-specific epitopes, deposited at the Immune Epitope Database, that are targeted by neutralizing antibodies or recognized by T cells. We found about 300 of such B cell epitopes, which were largely overlapping, and could be grouped into 54 B cell epitope clusters sharing ≥ 7 residues. Most of the B cell epitope clusters map in the RBD domain (39 out of 54) and 20%, 50%, 37%, 44% and 57% of the total are mutated in SARS-CoV-2 Alpha, Beta, Gamma, Delta and Omicron variants, respectively. We also found 234 experimentally verified CD8 and CD4 T cell epitopes that were distributed evenly throughout the spike protein. Interestingly, in each SARS-CoV-2 VOC, over 87% and 79% of CD8 and CD4 T cell epitopes, respectively, are not mutated. These observations suggest that SARS-CoV-2 VOCs—particularly the Omicron variant—may be prone to escape spike-specific antibody immunity, but not cellular immunity, elicited by COVID-19 vaccines. Full article
(This article belongs to the Special Issue State-of-the-Art Immunology and Immunotherapy in Europe)
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Review

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18 pages, 1278 KiB  
Review
The Role of Pericytes in Regulation of Innate and Adaptive Immunity
by Siarhei A. Dabravolski, Elena R. Andreeva, Ilya I. Eremin, Alexander M. Markin, Irina I. Nadelyaeva, Alexander N. Orekhov and Alexandra A. Melnichenko
Biomedicines 2023, 11(2), 600; https://doi.org/10.3390/biomedicines11020600 - 17 Feb 2023
Cited by 10 | Viewed by 2860
Abstract
Pericytes are perivascular multipotent cells wrapping microvascular capillaries, where they support vasculature functioning, participate in tissue regeneration, and regulate blood flow. However, recent evidence suggests that in addition to traditionally credited structural function, pericytes also manifest immune properties. In this review, we summarise [...] Read more.
Pericytes are perivascular multipotent cells wrapping microvascular capillaries, where they support vasculature functioning, participate in tissue regeneration, and regulate blood flow. However, recent evidence suggests that in addition to traditionally credited structural function, pericytes also manifest immune properties. In this review, we summarise recent data regarding pericytes’ response to different pro-inflammatory stimuli and their involvement in innate immune responses through expression of pattern-recognition receptors. Moreover, pericytes express various adhesion molecules, thus regulating trafficking of immune cells across vessel walls. Additionally, the role of pericytes in modulation of adaptive immunity is discussed. Finally, recent reports have suggested that the interaction with cancer cells evokes immunosuppression function in pericytes, thus facilitating immune evasion and facilitating cancer proliferation and metastasis. However, such complex and multi-faceted cross-talks of pericytes with immune cells also suggest a number of potential pericyte-based therapeutic methods and techniques for cancer immunotherapy and treatment of autoimmune and auto-inflammatory disorders. Full article
(This article belongs to the Special Issue State-of-the-Art Immunology and Immunotherapy in Europe)
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18 pages, 860 KiB  
Review
The Interplay of Tumor Vessels and Immune Cells Affects Immunotherapy of Glioblastoma
by Mitrajit Ghosh, Anna M. Lenkiewicz and Bozena Kaminska
Biomedicines 2022, 10(9), 2292; https://doi.org/10.3390/biomedicines10092292 - 15 Sep 2022
Cited by 10 | Viewed by 3639
Abstract
Immunotherapies with immune checkpoint inhibitors or adoptive cell transfer have become powerful tools to treat cancer. These treatments act via overcoming or alleviating tumor-induced immunosuppression, thereby enabling effective tumor clearance. Glioblastoma (GBM) represents the most aggressive, primary brain tumor that remains refractory to [...] Read more.
Immunotherapies with immune checkpoint inhibitors or adoptive cell transfer have become powerful tools to treat cancer. These treatments act via overcoming or alleviating tumor-induced immunosuppression, thereby enabling effective tumor clearance. Glioblastoma (GBM) represents the most aggressive, primary brain tumor that remains refractory to the benefits of immunotherapy. The immunosuppressive immune tumor microenvironment (TME), genetic and cellular heterogeneity, and disorganized vasculature hinder drug delivery and block effector immune cell trafficking and activation, consequently rendering immunotherapy ineffective. Within the TME, the mutual interactions between tumor, immune and endothelial cells result in the generation of positive feedback loops, which intensify immunosuppression and support tumor progression. We focus here on the role of aberrant tumor vasculature and how it can mediate hypoxia and immunosuppression. We discuss how immune cells use immunosuppressive signaling for tumor progression and contribute to the development of resistance to immunotherapy. Finally, we assess how a positive feedback loop between vascular normalization and immune cells, including myeloid cells, could be targeted by combinatorial therapies with immune checkpoint blockers and sensitize the tumor to immunotherapy. Full article
(This article belongs to the Special Issue State-of-the-Art Immunology and Immunotherapy in Europe)
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