Immune-Related Biomarkers II

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Biomarkers".

Deadline for manuscript submissions: 30 June 2024 | Viewed by 7636

Special Issue Editors

Chair of Physiology, Department of Veterinary Sciences, LMU Munich, D-82152 Martinsried, Germany
Interests: inflammation; innate immunity; cellular immunology; animal physiology; immunology; physiology; molecular biology; biotechnology; cell biology; cell culture
Special Issues, Collections and Topics in MDPI journals
Neurology Department, Center for Translational Neuro- and Behavioral Sciences (C-TNBS), Universitätsklinikum Essen, Hufelandstr. 55, 45147 Essen, Germany
Interests: neuroimmunology; multiple sclerosis (clinical/experimental); animal models; glial cells; immune tolerance
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Following a very successful first run, we are pleased to announce the launch of a second edition of the Special Issue “Immune-Related Biomarkers”.

In recent years, there has been a paradigm shift in the view of the immune system's involvement in many diseases.

The immune system is now known to be involved in many more diseases and to play a more important role in diseases occurring in old age than initially assumed. Its significance is becoming more apparent in diseases that were thought to be consequences of purely degenerative processes; many also have an active inflammatory component or are triggered by immune system reactions. The immune system is controlled by an intricate network of interacting signaling pathways and processes, many of which remain incompletely understood. Biomarkers for the stratification of different diseases or as generalized markers of a dysfunctional immune system should be used as a non-invasive molecular technology to assist in the prediction, diagnosis, prevention, and treatment of a variety of diseases.

Therefore, we invite the submission of review articles focusing on biomarkers suitable for this purpose. Critical articles regarding the flood of biomarkers that have already been proposed but failed to deliver on their promises in precision medicine are also welcome. In addition, we welcome any original work that makes a significant contribution to technical advances—whether in sample preparation, analytical methods, or bioinformatics data analysis—or that contributes to a better understanding of disease in terms of prediction, diagnosis, prevention, and treatment.

We would like to point out that, at the moment, the scope of our journal is mainly focused on basic science, in vitro, in vivo, and pre-clinical research, while purely clinical studies are usually not processed.

Prof. Dr. Cornelia Deeg
Dr. Jelena Skuljec
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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. Biomolecules 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 2700 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

  • immune biomarker
  • proteomics
  • O-link
  • molecular medicine
  • prediction of disease
  • diagnosis/stratification of diseases
  • targeted immune therapy

Related Special Issue

Published Papers (8 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review

13 pages, 3573 KiB  
Article
Triptolide Administration Alters Immune Responses to Mitigate Insulin Resistance in Obese States
by Lyudmila Grodsky, Mickey Wilson, Thirumurugan Rathinasabapathy and Slavko Komarnytsky
Biomolecules 2024, 14(4), 395; https://doi.org/10.3390/biom14040395 - 25 Mar 2024
Viewed by 254
Abstract
Individuals who are overweight or obese are at increased risk of developing prediabetes and type 2 diabetes, yet the direct molecular mechanisms that connect diabetes to obesity are not clear. Chronic, sustained inflammation is considered a strong risk factor in these interactions, directed [...] Read more.
Individuals who are overweight or obese are at increased risk of developing prediabetes and type 2 diabetes, yet the direct molecular mechanisms that connect diabetes to obesity are not clear. Chronic, sustained inflammation is considered a strong risk factor in these interactions, directed in part by the short-lived gene expression programs encoding for cytokines and pro-inflammatory mediators. In this study, we show that triptolide administration in the C57BL/6 diet-induced obese mice at up to 10 μg/kg/day for 10 weeks attenuated the development of insulin resistance and diabetes, but not obesity, in these animals. Significant reductions in adipose tissue inflammation and improved insulin sensitivity were observed in the absence of changes in food intake, body weight, body composition, or energy expenditure. Analysis of the core cluster of biomarkers that drives pro-inflammatory responses in the metabolic tissues suggested TNF-α as a critical point that affected the co-development of inflammation and insulin resistance, but also pointed to the putatively protective roles of increased COX-2 and IL-17A signaling in the mediation of these pathophysiological states. Our results show that reduction of diet-induced inflammation confers partial protection against insulin resistance, but not obesity, and suggest the possibility of achieving overweight phenotypes that are accompanied by minimal insulin resistance if inflammation is controlled. Full article
(This article belongs to the Special Issue Immune-Related Biomarkers II)
Show Figures

Figure 1

34 pages, 30581 KiB  
Article
Identifying OGN as a Biomarker Covering Multiple Pathogenic Pathways for Diagnosing Heart Failure: From Machine Learning to Mechanism Interpretation
by Yihao Zhu, Bin Chen and Yao Zu
Biomolecules 2024, 14(2), 179; https://doi.org/10.3390/biom14020179 - 02 Feb 2024
Viewed by 922
Abstract
Background: The pathophysiologic heterogeneity of heart failure (HF) necessitates a more detailed identification of diagnostic biomarkers that can reflect its diverse pathogenic pathways. Methods: We conducted weighted gene and multiscale embedded gene co-expression network analysis on differentially expressed genes obtained from HF and [...] Read more.
Background: The pathophysiologic heterogeneity of heart failure (HF) necessitates a more detailed identification of diagnostic biomarkers that can reflect its diverse pathogenic pathways. Methods: We conducted weighted gene and multiscale embedded gene co-expression network analysis on differentially expressed genes obtained from HF and non-HF specimens. We employed a machine learning integration framework and protein–protein interaction network to identify diagnostic biomarkers. Additionally, we integrated gene set variation analysis, gene set enrichment analysis (GSEA), and transcription factor (TF)-target analysis to unravel the biomarker-dominant pathways. Leveraging single-sample GSEA and molecular docking, we predicted immune cells and therapeutic drugs related to biomarkers. Quantitative polymerase chain reaction validated the expressions of biomarkers in the plasma of HF patients. A two-sample Mendelian randomization analysis was implemented to investigate the causal impact of biomarkers on HF. Results: We first identified COL14A1, OGN, MFAP4, and SFRP4 as candidate biomarkers with robust diagnostic performance. We revealed that regulating biomarkers in HF pathogenesis involves TFs (BNC2, MEOX2) and pathways (cell adhesion molecules, chemokine signaling pathway, cytokine–cytokine receptor interaction, oxidative phosphorylation). Moreover, we observed the elevated infiltration of effector memory CD4+ T cells in HF, which was highly related to biomarkers and could impact immune pathways. Captopril, aldosterone antagonist, cyclopenthiazide, estradiol, tolazoline, and genistein were predicted as therapeutic drugs alleviating HF via interactions with biomarkers. In vitro study confirmed the up-regulation of OGN as a plasma biomarker of HF. Mendelian randomization analysis suggested that genetic predisposition toward higher plasma OGN promoted the risk of HF. Conclusions: We propose OGN as a diagnostic biomarker for HF, which may advance our understanding of the diagnosis and pathogenesis of HF. Full article
(This article belongs to the Special Issue Immune-Related Biomarkers II)
Show Figures

Figure 1

20 pages, 2918 KiB  
Article
Defining Melanoma Immune Biomarkers—Desert, Excluded, and Inflamed Subtypes—Using a Gene Expression Classifier Reflecting Intratumoral Immune Response and Stromal Patterns
by Agata Mlynska, Jolita Gibavičienė, Otilija Kutanovaitė, Linas Senkus, Julija Mažeikaitė, Ieva Kerševičiūtė, Vygantė Maskoliūnaitė, Neda Rupeikaitė, Rasa Sabaliauskaitė, Justina Gaiževska, Karolina Suveizdė, Jan Aleksander Kraśko, Neringa Dobrovolskienė, Emilija Paberalė, Eglė Žymantaitė and Vita Pašukonienė
Biomolecules 2024, 14(2), 171; https://doi.org/10.3390/biom14020171 - 31 Jan 2024
Viewed by 670
Abstract
The spatial distribution of tumor infiltrating lymphocytes (TILs) defines several histologically and clinically distinct immune subtypes—desert (no TILs), excluded (TILs in stroma), and inflamed (TILs in tumor parenchyma). To date, robust classification of immune subtypes still requires deeper experimental evidence across various cancer [...] Read more.
The spatial distribution of tumor infiltrating lymphocytes (TILs) defines several histologically and clinically distinct immune subtypes—desert (no TILs), excluded (TILs in stroma), and inflamed (TILs in tumor parenchyma). To date, robust classification of immune subtypes still requires deeper experimental evidence across various cancer types. Here, we aimed to investigate, define, and validate the immune subtypes in melanoma by coupling transcriptional and histological assessments of the lymphocyte distribution in tumor parenchyma and stroma. We used the transcriptomic data from The Cancer Genome Atlas melanoma dataset to screen for the desert, excluded, and inflamed immune subtypes. We defined subtype-specific genes and used them to construct a subtype assignment algorithm. We validated the two-step algorithm in the qPCR data of real-world melanoma tumors with histologically defined immune subtypes. The accuracy of a classifier encompassing expression data of seven genes (immune response-related: CD2, CD53, IRF1, and CD8B; and stroma-related: COL5A2, TNFAIP6, and INHBA) in a validation cohort reached 79%. Our findings suggest that melanoma tumors can be classified into transcriptionally and histologically distinct desert, excluded, and inflamed subtypes. Gene expression-based algorithms can assist physicians and pathologists as biomarkers in the rapid assessment of a tumor immune microenvironment while serving as a tool for clinical decision making. Full article
(This article belongs to the Special Issue Immune-Related Biomarkers II)
Show Figures

Figure 1

26 pages, 11149 KiB  
Article
Construction of a Novel Damage-Associated Molecular-Pattern-Related Signature to Assess Lung Adenocarcinoma’s Prognosis and Immune Landscape
by Xinyue Liu, Shuxi Yao, Yanqi Feng, Piao Li, Yiming Li and Shu Xia
Biomolecules 2024, 14(1), 108; https://doi.org/10.3390/biom14010108 - 15 Jan 2024
Viewed by 869
Abstract
Immunogenic death (ICD) stimulates adaptive immunity and affects immunotherapeutic efficacy, an important part of which is damage-associated molecular patterns (DAMPs). However, the function of these DAMPs for lung adenocarcinoma (LUAD) remains obscure. We initially found differentially expressed genes (DEGs) with prognostic significance related [...] Read more.
Immunogenic death (ICD) stimulates adaptive immunity and affects immunotherapeutic efficacy, an important part of which is damage-associated molecular patterns (DAMPs). However, the function of these DAMPs for lung adenocarcinoma (LUAD) remains obscure. We initially found differentially expressed genes (DEGs) with prognostic significance related to DAMPs with the TCGA database and then used the least absolute shrinkage and selection operator (LASSO) regression to create a risk signature strongly correlated with overall survival (OS) with eight DEGs. Validation was performed externally using the external data set GSE68465. Lower-risk LUAD patients were found to be more chemotherapy-resistant and enriched for more immune-related pathways than those with higher risk scores, and patients with different risks showed different levels of immune cell infiltration. PANX1, a crucial gene closely associated with lung adenocarcinoma, was identified using the weighted correlation network analysis (WGCNA), and experiments revealed that PANX1 promotes the proliferation as well as invasion of LUAD cells. Furthermore, PANX1 was found to be positively correlated with CD274, CD276, and M2 macrophage markers. We developed and validated an entirely new gene signature related to DAMPs that may be useful for LUAD patient prognosis, immune microenvironment, and chemotherapeutic drug sensitivity prediction. The results may also guide clinical immunotherapy and chemotherapy approaches for LUAD patients. Full article
(This article belongs to the Special Issue Immune-Related Biomarkers II)
Show Figures

Figure 1

17 pages, 14861 KiB  
Article
Exosome-Related FTCD Facilitates M1 Macrophage Polarization and Impacts the Prognosis of Hepatocellular Carcinoma
by Youyi Liu, Yifei Tang, Hongliang Jiang, Xiading Zhang, Xingyi Chen, Jingrou Guo, Cheng Jin and Minchen Wu
Biomolecules 2024, 14(1), 41; https://doi.org/10.3390/biom14010041 - 28 Dec 2023
Cited by 1 | Viewed by 1011
Abstract
Background: Exosomes are essential for hepatocellular carcinoma (HCC) progression and have garnered significant interest as novel targets for diagnostic, prognostic, and therapeutic approaches. This study aims to identify potential exosome-related biomarkers for the development of useful strategies for HCC diagnosis and therapy. Methods: [...] Read more.
Background: Exosomes are essential for hepatocellular carcinoma (HCC) progression and have garnered significant interest as novel targets for diagnostic, prognostic, and therapeutic approaches. This study aims to identify potential exosome-related biomarkers for the development of useful strategies for HCC diagnosis and therapy. Methods: Three datasets obtained from the Gene Expression Omnibus (GEO) were utilized to identify differentially expressed genes (DEGs) in HCC. Through Gene Ontology (GO) analysis and protein–protein interaction (PPI) network, overall survival (OS) analysis, Cox analyses, and diethylnitrosamine (DEN)-induced HCC mouse model detection, exosome-related hub gene was screened out, followed by a prognostic value assessment and immune-correlates analysis based on the Cancer Genome Atlas (TCGA) dataset. The hub gene-containing exosomes derived from Hepa1-6 cells were isolated and characterized using differential ultracentrifugation, transmission electron microscopy scanning, and Western blot. Ultrasound-guided intrahepatic injection, cell co-culture, CCK-8, and flow cytometry were performed to investigate the effects of the hub gene on macrophage infiltration and polarization in HCC. Results: A total of 83 DEGs enriched in the extracellular exosome term, among which, FTCD, HRA, and C8B showed the strongest association with the progression of HCC. FTCD was independently associated with a protective effect in HCC and selected as the hub gene. The presence of FTCD in exosomes was confirmed. FTCD-stimulated macrophages were polarized towards the M1 type and suppressed HCC cells proliferation. Conclusions: FTCD is a potential exosome-related biomarker for HCC diagnosis, prognosis, and treatment. The crosstalk between FTCD-containing exosomes and macrophages in HCC progression deserves further investigation. Full article
(This article belongs to the Special Issue Immune-Related Biomarkers II)
Show Figures

Graphical abstract

12 pages, 1287 KiB  
Article
Association of Asymmetric and Symmetric Dimethylarginine with Inflammation in the Population-Based Study of Health in Pomerania
by Martin Sebastian Winkler, Martin Bahls, Rainer H. Böger, Till Ittermann, Marcus Dörr, Nele Friedrich and Edzard Schwedhelm
Biomolecules 2023, 13(11), 1612; https://doi.org/10.3390/biom13111612 - 04 Nov 2023
Viewed by 902
Abstract
The amino acids arginine (Arg), asymmetric (ADMA) and symmetric dimethylarginine (SDMA) are related to nitric oxide (NO) metabolism and potential markers of two different disease entities: cardiovascular disease such as atherosclerosis and systemic inflammation in critically ill patients with sepsis. Although very different [...] Read more.
The amino acids arginine (Arg), asymmetric (ADMA) and symmetric dimethylarginine (SDMA) are related to nitric oxide (NO) metabolism and potential markers of two different disease entities: cardiovascular disease such as atherosclerosis and systemic inflammation in critically ill patients with sepsis. Although very different in their pathophysiological genesis, both entities involve the functional integrity of blood vessels. In this context, large population-based data associating NO metabolites with proinflammatory markers, e.g., white blood cell count (WBC), high-sensitivity C-reactive protein (hsCRP), and fibrinogen, or cytokines are sparse. We investigated the association of Arg, ADMA and SDMA with WBC, hsCRP, and fibrinogen in 3556 participants of the Study of Health in Pomerania (SHIP)-TREND study. Furthermore, in a subcohort of 456 subjects, 31 inflammatory markers and cytokines were analyzed. We identified Arg and SDMA to be positively associated with hsCRP (β coefficient 0.010, standard error (SE) 0.002 and 0.298, 0.137, respectively) as well as fibrinogen (β 5.23 × 10−3, SE 4.75 × 10−4 and 0.083, 0.031, respectively). ADMA was not associated with WBC, hsCRP, or fibrinogen. Furthermore, in the subcohort, Arg was inversely related to a proliferation-inducing ligand (APRIL). SDMA was positively associated with osteocalcin, tumor necrosis factor receptor 1 and 2, and soluble cluster of differentiation 30. Our findings provide new insights into the involvement of Arg, ADMA, and SDMA in subclinical inflammation in the general population. Full article
(This article belongs to the Special Issue Immune-Related Biomarkers II)
Show Figures

Figure 1

Review

Jump to: Research

20 pages, 2517 KiB  
Review
LILRB4 Checkpoint for Immunotherapy: Structure, Mechanism and Disease Targets
by Zhiqing Xiang, Xiangli Yin, Leiyan Wei, Manqing Peng, Quan Zhu, Xiaofang Lu, Junshuang Guo, Jing Zhang, Xin Li and Yizhou Zou
Biomolecules 2024, 14(2), 187; https://doi.org/10.3390/biom14020187 - 04 Feb 2024
Viewed by 886
Abstract
LILRB4, a myeloid inhibitory receptor belonging to the family of leukocyte immunoglobulin-like receptors (LILRs/LIRs), plays a pivotal role in the regulation of immune tolerance. LILRB4 primarily mediates suppressive immune responses by transmitting inhibitory signals through immunoreceptor tyrosine-based inhibitory motifs (ITIMs). This immune checkpoint [...] Read more.
LILRB4, a myeloid inhibitory receptor belonging to the family of leukocyte immunoglobulin-like receptors (LILRs/LIRs), plays a pivotal role in the regulation of immune tolerance. LILRB4 primarily mediates suppressive immune responses by transmitting inhibitory signals through immunoreceptor tyrosine-based inhibitory motifs (ITIMs). This immune checkpoint molecule has gained considerable attention due to its potent regulatory functions. Its ability to induce effector T cell dysfunction and promote T suppressor cell differentiation has been demonstrated, indicating the therapeutic potential of LILRB4 for modulating excessive immune responses, particularly in autoimmune diseases or the induction of transplant tolerance. Additionally, through intervening with LILRB4 molecules, immune system responsiveness can be adjusted, representing significant value in areas such as cancer treatment. Thus, LILRB4 has emerged as a key player in addressing autoimmune diseases, transplant tolerance induction, and other medical issues. In this review, we provide a comprehensive overview of LILRB4, encompassing its structure, expression, and ligand molecules as well as its role as a tolerance receptor. By exploring the involvement of LILRB4 in various diseases, its significance in disease progression is emphasized. Furthermore, we propose that the manipulation of LILRB4 represents a promising immunotherapeutic strategy and highlight its potential in disease prevention, treatment and diagnosis. Full article
(This article belongs to the Special Issue Immune-Related Biomarkers II)
Show Figures

Figure 1

15 pages, 719 KiB  
Review
Neutrophil-to-Lymphocyte Ratio (NLR) in NSCLC, Gastrointestinal, and Other Solid Tumors: Immunotherapy and Beyond
by Mirta Mosca, Maria Concetta Nigro, Rachele Pagani, Andrea De Giglio and Alessandro Di Federico
Biomolecules 2023, 13(12), 1803; https://doi.org/10.3390/biom13121803 - 18 Dec 2023
Cited by 1 | Viewed by 1506
Abstract
In the era of immunotherapy, identifying biomarkers of immune system activation has become a high-priority challenge. The blood neutrophil-to-lymphocyte ratio (NLR) has been largely investigated as a biomarker in several cancer types. NLR values have been shown to mirror the tumor-induced inflammatory status [...] Read more.
In the era of immunotherapy, identifying biomarkers of immune system activation has become a high-priority challenge. The blood neutrophil-to-lymphocyte ratio (NLR) has been largely investigated as a biomarker in several cancer types. NLR values have been shown to mirror the tumor-induced inflammatory status and have been demonstrated to be a reliable prognostic tool across stages of disease and therapeutic approaches. When integrated with other biomarkers of response to immunotherapy, such as PD-L1, tumor mutational burden, and tumor-associated immune cells, the NLR may allow to further stratify patients with different likelihoods of deriving a significant clinical benefit. However, despite its accessibility, low cost, and easy interpretation, the NLR is still poorly used as a prognostic tool in daily clinical practice. In this review, we analyze the role of the NLR in defining the relationship between cancer and the immune system, its usefulness in daily clinical practice, and its relationship with other established or emerging biomarkers of immunotherapy outcomes. Full article
(This article belongs to the Special Issue Immune-Related Biomarkers II)
Show Figures

Figure 1

Back to TopTop