Article
Immunology
Jie Shen, Mengyu Zhang, Ke Zhang, Yahan Qin, Meifang Liu, Shujuan Liang, Daquan Chen, Meiyu Peng
Summary: This study found that Angelica polysaccharide (APS) promoted the proliferation, differentiation, and immunosuppressive function of myeloid-derived suppressor cells (MDSC) through the STAT1 and STAT3 signaling pathways. In vivo, APS increased the proportion of MDSC in mice, suggesting that its clinical application should consider the possible side effects of increasing MDSC quantity and function.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Medicine, Research & Experimental
Qinxin Liu, Yuchang Wang, Qiang Zheng, Xijie Dong, Zhenxing Xie, Adriana Panayi, Xiangjun Bai, Zhanfei Li
Summary: The study revealed that miR-150 is down-regulated during sepsis, replenishing miR-150 can reduce the immunosuppression function of MDSCs by down-regulating ARG1 in late sepsis, and has impacts on both pro-inflammatory and anti-inflammatory cytokines. In humans, the level of miR-150 is associated with health and different inflammatory states.
Article
Immunology
Lili Ding, Minjie Wan, Dong Wang, Huiru Cao, Haijiao Wang, Pujun Gao
Summary: Acute pancreatitis (AP) is pancreatic or systemic inflammation, and severe acute pancreatitis (SAP) is the main cause of death for AP patients. This study found that MDSCs (myeloid-derived suppressor cells) were increased in AP patients, especially in SAP patients, and their frequency was positively correlated with disease severity. The MDSCs from SAP patients exhibited enhanced suppressive ability, which might be attributed to the overexpression of Arg-1 and ROS.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Samantha L. Tucker, Demba Sarr, Balazs Rada
Summary: Cystic Fibrosis is a genetic disease that causes chronic lung inflammation and infections, leading to high mortality rates. Immune system disruption in CF results in impaired immune responses, chronic infections with pathogens, and alterations in T cell and neutrophil functions. The role of P. aeruginosa and gMDSCs in T cell suppression and immune evasion in CF remains a subject of ongoing research.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Cell Biology
Subhajit Ghosh, Jiayi Huang, Matthew Inkman, Jin Zhang, Sukrutha Thotala, Ekaterina Tikhonova, Natalia Miheecheva, Felix Frenkel, Ravshan Ataullakhanov, Xiaowei Wang, David DeNardo, Dennis Hallahan, Dinesh Thotala
Summary: Severe and prolonged lymphopenia often occurs in glioblastoma patients after standard chemoradiotherapy, and it is associated with worse survival. A correlative study was conducted on 20 patients with glioblastoma to investigate the underlying biological mechanism of lymphopenia. The study revealed an elevated concentration of myeloid-derived suppressor cell (MDSC) regulatory genes in patients with lymphopenia after chemoradiotherapy. Further analysis confirmed increased numbers of circulating MDSC in these patients, and preclinical models demonstrated a causal relationship between radiation-induced MDSC and systemic lymphopenia. Pharmacological inhibition of MDSC effectively prevented radiation-induced lymphopenia and improved survival in the models, suggesting the potential of CB1158 and tadalafil as drugs for reducing lymphopenia in glioblastoma patients.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Review
Cell Biology
Vaishali Bhardwaj, Stephen M. M. Ansell
Summary: Myeloid-derived suppressor cells (MDSCs) are immunosuppressive cells composed of pathologically activated neutrophils and monocytes that negatively regulate the immune response to cancer and chronic infections. They exhibit distinct characteristics and exert strong immunosuppressive effects on T-cells and other immune cells, making them a major obstacle to cancer immunotherapies. However, the clinical outcomes of targeting MDSCs in hematological malignancies, particularly B-cell malignancies, still require further exploration. This review provides a comprehensive summary of the complex biology and immunosuppressive pathways of MDSCs, with a focus on their role in modulating T-cell function in hematological malignancies, and discusses the challenges, therapeutic strategies, and clinical relevance of targeting MDSCs in these diseases.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Review
Medicine, General & Internal
Suncica Kapor, Juan F. Santibanez
Summary: This review discusses the main features of MDSCs and MSCs in myeloid malignancies, revealing that MDSCs are elevated in numbers and exhibit strong immunosuppressive capabilities, while MSCs not only have immunosuppressive properties but also regulate the growth, apoptosis, and chemotherapy resistance of myeloid leukemia cells.
JOURNAL OF CLINICAL MEDICINE
(2021)
Review
Immunology
Yudan Cui, Jingshan Cai, Wenxin Wang, Shengjun Wang
Summary: HDACIs are antitumor drugs that enhance gene transcription via epigenetic regulation, with cytotoxic properties against tumor cells. The effects of HDACIs on immunocytes in the tumor microenvironment, specifically MDSCs, are still not fully understood.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Chiel van Geffen, Astrid Deissler, Sandra Beer-Hammer, Bernd Nuernberg, Rupert Handgretinger, Harald Renz, Dominik Hartl, Saeed Kolahian
Summary: The study suggests that MDSCs play a role in lung diseases like asthma through the EP4 pathway, showing that EP4-primed MDSCs can dampen airway inflammation by modulating arginase-1 and nitric oxide synthase-2.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Maria Iglesias-Escudero, David San Segundo, David Merino-Fernandez, Victor M. Mora-Cuesta, Patricia Lamadrid, Marta Alonso-Pena, Sandra Raso, David Iturbe, Sonia Fernandez-Rozas, Jose Cifrian, Marcos Lopez-Hoyos
Summary: Lung transplantation is a primary treatment for end-stage lung diseases, but long-term survival is limited. The study explores the dysregulation of immune mechanisms and the role of myeloid-derived suppressor cells (MDSCs) in promoting graft tolerance. The results suggest that increased frequencies of Mo-MDSCs after acute cellular rejection may be associated with the development of chronic lung allograft dysfunction (CLAD).
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Jingshan Cai, Yudan Cui, Jun Yang, Shengjun Wang
Summary: MDSCs play a crucial role in tumor immunity, closely linked to tumor EMT and possessing unique functions in an immunosuppressive environment.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2021)
Review
Immunology
Manuel Fresno, Nuria Girones
Summary: MDSCs, immature myeloid cells that expand under pathological conditions, are characterized by their suppressor activity and can express iNOS and arginase 1 for immune suppression. They can originate from the medulla due to emergency myelopoiesis, but can also have extramedullary origins.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Review
Immunology
Maria Luisa Sanchez-Leon, Carlos Jimenez-Cortegana, Gabriel Cabrera, Elba Monica Vermeulen, Luis de la Cruz-Merino, Victor Sanchez-Margalet
Summary: Dendritic cells (DCs) play a diminished role in various malignancies due to immunosuppressive conditions in the tumor microenvironment (TME). Myeloid-derived suppressor cells (MDSCs) accumulate in the TME and inhibit DC functions, maturation, and development. DC-based vaccines have been developed to improve antitumor immunity, and their effectiveness in murine models and cancer patients, alone or in combination with other treatments, has been explored.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Ying He, Sze Wan Hung, Bo Liang, Ruizhe Zhang, Yating Gao, Ching Yan Chu, Tao Zhang, Hui Xu, Jacqueline Pui Wah Chung, Chi Chiu Wang
Summary: The study demonstrated that Sunitinib inhibited endometriotic lesions by promoting the maturation of MDSCs and inhibiting immunosuppressive functions, showing potential therapeutic effects for treating endometriosis.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Yuze Wu, Ming Yi, Mengke Niu, Qi Mei, Kongming Wu
Summary: This review focuses on the classification and inhibitory function of myeloid-derived suppressor cells (MDSCs) in immune checkpoint inhibitor (ICI) therapy, as well as the crosstalk between MDSCs and other myeloid cells. Recent findings suggest that targeting MDSCs may be a promising approach to enhance the efficacy of cancer immunotherapy.
Article
Medicine, Research & Experimental
Marco Erreni, Francesca D'Autilia, Roberta Avigni, Evangelia Bolli, Sana M. Arnouk, Kiavash Movahedi, Pieterjan Debie, Achille Anselmo, Raffaella Parente, Cecile Vincke, Fijs W. B. van Leeuwen, Paola Allavena, Cecilia Garlanda, Alberto Mantovani, Andrea Doni, Sophie Hernot, Jo A. Van Ginderachter
Summary: Nanobodies (Nbs) have been identified as an elegant alternative to conventional monoclonal antibodies for cancer therapy, but there is a lack of detailed microscopic insight into the in vivo pharmacokinetics of different Nb formats in tumor-bearers, especially for the targeting of pro-tumoral tumor-associated macrophages (TAMs) located in less penetrable tumor regions.
Review
Oncology
Romina Mora Barthelmess, Benoit Stijlemans, Jo A. Van Ginderachter
Summary: The aim of this review is to summarize the available information regarding the MIF family in cancer. MIF and DDT are both highly expressed in cancer patients and their functions are related to 9 out of 10 hallmarks of cancer, indicating their potential as therapeutic targets. New diagnostic methods and treatments have decreased the mortality rates of cancer patients, but further improvements are warranted based on the identification of novel tumor-promoting molecules.
Article
Multidisciplinary Sciences
Rute Goncalves, Joana Couto, Pedro Ferreirinha, Jose Maria Costa, Diogo Silverio, Marta L. Silva, Ana Isabel Fernandes, Pedro Madureira, Nuno L. Alves, Sofia Lamas, Margarida Saraiva
Summary: In this study, the k18-hACE2 mouse model was used to investigate the relationship between SARS-CoV-2 variants alpha, delta, and omicron and tissue pathology and immune response. We found that different variants had distinct patterns of infection severity, affecting lung and blood immune responses and primary lymphoid organs differently. Infections with alpha and delta variants promoted bone marrow emergency myelopoiesis, resulting in increased levels of neutrophils in the blood and lungs. Importantly, the changes in immune responses correlated with the severity of infection. This study provides a comprehensive platform to study the modulation of disease by SARS-CoV-2 variants and highlights the impact of this infection on the function of primary lymphoid organs.
Article
Medicine, Research & Experimental
Joao Moreria, Helena Martins, Margarida Saraiva, Maria Joao Saraiva
Summary: Hereditary amyloid transthyretin (ATTRv) amyloidosis is a fatal neurodegenerative disease characterized by extracellular deposition of mutant transthyretin (TTR) forms in the peripheral nervous system. This study shows a down-regulation of chemokine expression and p38 MAP kinase phosphorylation in V30M macrophages, contributing to the impaired inflammatory responses observed in ATTRv patients. These findings provide new insights for understanding the molecular mechanisms underlying ATTRv and may aid in the development of immune therapeutic strategies.
Article
Biochemistry & Molecular Biology
Yolanda Prado, Cesar Echeverria, Carmen G. G. Feijoo, Claudia A. A. Riedel, Claudio Cabello-Verrugio, Juan F. F. Santibanez, Felipe Simon
Summary: Sepsis syndrome is characterized by enhanced secretion of pro-inflammatory cytokines and reactive oxygen species, leading to vascular hyperpermeability, hypotension, multiple organ dysfunction syndrome (MODS), and increased mortality. Endotoxemia-derived sepsis plays an important role in sepsis syndrome, where endotoxin interacts with endothelial cells and induces detrimental effects. Nutrient consumption, including omega-3 fatty acids, ascorbic acid, and polyphenolic antioxidant flavonoids, modulates the progression of sepsis. This study aimed to investigate the impact of dietary supplementation with these nutrients on the modulation of fibrotic endothelial gene-expression patterns during sepsis and their effects on sepsis outcomes. The findings suggest that the consumption of omega-3 fatty acids and polyphenolic antioxidant flavonoids improves endotoxemia outcomes, highlighting the potential role of specific nutrient consumption in sepsis treatment.
Review
Immunology
Neema Ahishakiye Jumapili, Maida Zivalj, Romina Mora Barthelmess, Geert Raes, Timo W. M. De Groof, Nick Devoogdt, Benoit Stijlemans, Cecile Vincke, Jo A. Van Ginderachter
Summary: mAbs have limitations in their distribution and penetration in tumor microenvironment, as well as their ability to reach the brain. Nanobodies, being smaller in size, possess superior abilities in tumor penetration and infiltration into brain tumors. However, the rapid clearance of nanobodies from circulation may affect their suitability for therapy, although their noncovalent binding to albumin can help increase their serum half-life.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Odrade Gondry, Catarina Xavier, Laurens Raes, Johannes Heemskerk, Nick Devoogdt, Hendrik Everaert, Karine Breckpot, Quentin Lecocq, Lore Decoster, Christel Fontaine, Denis Schallier, Sandrine Aspeslagh, Ilse Vaneycken, Geert Raes, Jo A. Van Ginderachter, Tony Lahoutte, Vicky Caveliers, Marleen Keyaerts
Summary: Macrophages play a vital role in the body, and anti-inflammatory macrophages targeting CD206 are involved in various diseases. This study evaluated the safety and biodistribution of a PET tracer targeting CD206 in human subjects, and found that the tracer was safe, rapidly cleared from the blood, and enabled high contrast imaging at 90 minutes after injection. Preliminary results showed higher tumor uptake in patients with disease progression.
JOURNAL OF NUCLEAR MEDICINE
(2023)
Article
Immunology
Emile J. Clappaert, Daliya Kancheva, Jan Brughmans, Ayla Debraekeleer, Pauline M. R. Bardet, Yvon Elkrim, Dagmar Lacroix, Maida Zivalj, Ahmed E. I. Hamouda, Jo A. Van Ginderachter, Sofie Deschoemaeker, Damya Laoui
Summary: This study found that while Flt3L treatment can increase all cDC subsets in the tumor, it does not reduce tumor growth in any of the models. In addition, in some cases, Flt3L treatment also leads to an increase in CD81(+)migcDC1 subset, which has Treg-inducing potential. Overall, increasing cDC numbers in the tumor alone may not improve anti-tumor responses and may not be beneficial for cancer treatment.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Oncology
Maida Zivalj, Jo A. Van Ginderachter, Benoit Stijlemans
Summary: The aim of this review is to summarize the available information regarding Lipocalin-2 in tumor progression. Lipocalin-2 expression is correlated with tumorigenesis and can be considered as a biomarker and potential drug target in cancer therapy.
Article
Immunology
Olivera Mitrovic-Ajtic, Dragoslava Dikic, Tijana Suboticki, Sandra Bizic-Radulovic, Bojana Beleslin-Cokic, Teodora Dragojevic, Emilija Zivkovic, Sanja Miljatovic, Milica Vukotic, Dejana Stanisavljevic, Juan Santibanez, Vladan P. Cokic
Summary: The severity and mortality of COVID-19 are higher in males than in females, although the infection rate is the same. This study found that male patients with COVID-19 had lower levels of testosterone and free testosterone, while female patients had increased levels of tumor necrosis factor-alpha. Sex hormones may play a protective role during SARS-CoV-2 infection, but impaired testosterone synthesis in men weakens this protective effect.
Article
Pharmacology & Pharmacy
Maximilian Scherger, Yannick A. A. Pilger, Judith Stickdorn, Patric Komforth, Sascha Schmitt, Sana M. M. Arnouk, Els Lebegge, Kaloian Koynov, Hans-Joachim Rader, Jo A. A. Van Ginderachter, Lutz Nuhn
Summary: In this study, a procedure is demonstrated for site-specific reversible bioconjugation of genetically engineered single domain antibodies, called nanobodies, using self-immolative linkers (SILs). The flow cytometry and microscopy images confirm cellular uptake and biological affinity of the modified nanobodies. This strategy can be extended to other therapeutically relevant representatives of nanobodies, highlighting the versatility of this reversible reductive-responsive bioconjugation in a broad field of applications.
ADVANCED THERAPEUTICS
(2023)
Article
Chemistry, Multidisciplinary
Rodrigo Ramirez-Tagle, Leonor Alvarado-Soto, Juan F. Santibanez, Cesar Echeverria
Summary: The relationship between the structural characteristic of curcumin and dimethoxycurcumin and their antitumor activity was investigated. Treatment of HepG2 cells with curcumin and dimethoxycurcumin for 24 hours induced apoptosis and inhibited cell proliferation in a dose-dependent manner. Docking and DFT calculations suggested a structure-activity relationship between the activities of dimethoxycurcumin and the structural characteristics of curcumin in inducing apoptosis in HepG2 cells.
Review
Cell Biology
Juan F. Santibanez, Cesar Echeverria, Carola Millan, Felipe Simon
Summary: This review provides an overview of the current knowledge on the mechanisms of the TGF-beta superfamily in MSCs bone differentiation and further insight into the mutual regulation of microRNAs and TGF-beta in osteogenesis.
Meeting Abstract
Clinical Neurology
Doruk Arslan, Zeynep Ergul-Ulger, Sibel Goksen, Gunes Esendagli, Sevim Erdem-Ozdamar, Ersin Tan, Can Ebru Bekircan-Kurt
Article
Multidisciplinary Sciences
Ece Tavukcuoglu, Hamdullah Yanik, Mubaida Parveen, Sila Uluturk, Mine Durusu-Tanriover, Ahmet Cagkan Inkaya, Murat Akova, Serhat Unal, Gunes Esendagli
Summary: This study evaluates the functional capacity of CD4(+) and CD8(+) memory T cells obtained from volunteers vaccinated with an aluminum-adjuvanted inactivated whole-virion SARS-CoV-2 vaccine. The results show that memory T cells from vaccinated individuals significantly proliferate and secrete IFN-γ in response to S1 stimulation.
SCIENTIFIC REPORTS
(2023)