Article
Oncology
Anna Sosnowska, Justyna Chlebowska-Tuz, Pawel Matryba, Zofia Pilch, Alan Greig, Artur Wolny, Tomasz M. Grzywa, Zuzanna Rydzynska, Olga Sokolowska, Tomasz P. Rygiel, Marcin Grzybowski, Paulina Stanczak, Roman Blaszczyk, Dominika Nowis, Jakub Golab
Summary: The research showed that Arg1 plays a key role in regulating the anti-tumor immune response. Inhibition of Arg1 can promote antigen-specific T cell proliferation and inhibit tumor growth. Arginase inhibitors modestly inhibit tumor growth and can significantly improve survival outcomes when combined with other treatment strategies.
Article
Biochemistry & Molecular Biology
Barbara Ersek, Palma Sillo, Ugur Cakir, Viktor Molnar, Andras Bencsik, Balazs Mayer, Eva Mezey, Sarolta Karpati, Zoltan Pos, Krisztian Nemeth
Summary: This study demonstrates that melanoma-associated fibroblasts suppress the activity of cytotoxic T lymphocytes, with a key role played by arginase. It was found that in the presence of MAF-conditioned media, CTL activation was disrupted, leading to dysregulated signaling and upregulation of immune checkpoint receptors. This interference is mediated by soluble factors and l-arginine depletion, ultimately resulting in CTL anergy and immune checkpoint modulation.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
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
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)
Article
Oncology
Stine Emilie Weis-Banke, Thomas Landkildehus Lisle, Maria Perez-Penco, Aimilia Schina, Mie Linder Hubbe, Majken Siersbaek, Morten Orebo Holmstrom, Mia Aaboe Jorgensen, Inge Marie Svane, Ozcan Met, Niels Odum, Daniel Hargbol Madsen, Marco Donia, Lars Grontved, Mads Hald Andersen
Summary: This study identified the presence of ARG2-specific CD8(+) T cells in both healthy donors and patients with cancer. These T cells are capable of recognizing and responding to cancer cells and activated Tregs with high ARG2 expression. Furthermore, vaccination with ARG2-derived epitopes in a mouse tumor model resulted in tumor growth suppression and antitumorigenic immunomodulation.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
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)
Article
Oncology
Marcin Mikolaj Grzybowski, Paulina Seweryna Stalczak, Paulina Pomper, Roman Blaszczyk, Bartlomiej Borek, Anna Gzik, Julita Nowicka, Karol Jedrzejczak, Joanna Brzezinska, Tomasz Rejczak, Nazan Cemre Guner-Chalimoniuk, Agnieszka Kikulska, Michal Mlacki, Jolanta Peczkowicz-Szyszka, Jacek Olczak, Adam Golebiowski, Karolina Dzwonek, Pawel Dobrzanski, Zbigniew Zaslona
Summary: This study validates the therapeutic benefits of pharmacological inhibition of ARG2 in cancer and presents OATD-02 as a potential treatment option with immunomodulatory and direct antitumour effects. OATD-02 has shown promise in combination with other immunotherapeutics and will enter clinical trials in cancer patients in 2022.
Review
Oncology
Laure Chardin, Alexandra Leary
Summary: Ovarian cancer is a highly lethal gynecologic malignancy with a high recurrence rate, despite many patients responding effectively to current treatments. In order to improve outcomes, further research into the immune microenvironment and the development of effective therapies are urgently needed.
FRONTIERS IN ONCOLOGY
(2021)
Review
Oncology
Thamiris Becker Scheffel, Nathalia Grave, Pedro Vargas, Fernando Mendonca Diz, Liliana Rockenbach, Fernanda Bueno Morrone
Summary: Glioblastoma is a highly malignant subtype of glioma, and the immune landscape within the tumor microenvironment plays a crucial role in influencing therapy outcomes. The presence of multiple immunosuppression pathways, particularly the adenosine pathway, poses significant obstacles to immune-based cancer therapies and can contribute to treatment resistance. Research focusing on immune checkpoints and the adenosine pathway may provide insights into potential targets for improving tumor treatment strategies.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Paulina Pilanc, Kamil Wojnicki, Adria-Jaume Roura, Salwador Cyranowski, Aleksandra Ellert-Miklaszewska, Natalia Ochocka, Bartlomiej Gielniewski, Marcin M. Grzybowski, Roman Blaszczyk, Paulina S. Stanczak, Pawel Dobrzanski, Bozena Kaminska
Summary: Glioblastomas are aggressive and incurable brain tumors due to the highly immunosuppressive tumor microenvironment. However, inhibition of arginase 1 and 2 may potentially unblock T cell suppression and show promise in treating glioblastomas.
FRONTIERS IN ONCOLOGY
(2021)
Article
Immunology
Guanning Wang, Masaki Tajima, Tasuku Honjo, Akio Ohta
Summary: Studies show that IL-2 inhibits the expression of PD-1, thereby enhancing the activity of CD8(+) T cells.
INTERNATIONAL IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Satu Salmi, Kaisla Halinen, Anton Lin, Sanna Suikkanen, Otto Jokelainen, Eija Rahunen, Hanna Siiskonen, Sanna Pasonen-Seppanen
Summary: In melanoma, CD8+ and GrB+ lymphocytes were found to be more abundant in pT4 melanomas and lymph node metastases compared to primaries. A low GrB/CD8 ratio was associated with better recurrence-free survival in primary melanomas, suggesting that GrB+ lymphocytes may represent activated immunosuppressive lymphocytes.
Review
Immunology
Changfa Sun, Bochu Wang, Shilei Hao
Summary: The adenosine-A2AR pathway plays a crucial role in regulating immune responses and tumor progression. Blocking this pathway can inhibit tumor growth and has potential synergistic effects with CAR T cell therapy.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Guanyu Wang, Jinpeng Wang, Chaoshi Niu, Yan Zhao, Pengfei Wu
Summary: This review focuses on the functional roles of neutrophils in glioma patients, discussing the mechanisms of neutrophil recruitment, immunosuppression, and differentiation. It also highlights the potential of neutrophils as clinical biomarkers and therapeutic targets, providing new insights for glioma treatment.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Pharmacology & Pharmacy
Mahmoud S. Alghamri, Brandon L. McClellan, Margaret S. Hartlage, Santiago Haase, Syed Mohd Faisal, Rohit Thalla, Ali Dabaja, Kaushik Banerjee, Stephen V. Carney, Anzar A. Mujeeb, Michael R. Olin, James J. Moon, Anna Schwendeman, Pedro R. Lowenstein, Maria G. Castro
Summary: Gliomas, particularly glioblastomas, are highly aggressive and lethal cancers with unique molecular characteristics and genetic signatures. The interactions between tumor cells and immune cells in the tumor microenvironment play a critical role in glioma progression. Understanding the impact of inflammation and potential pharmacological interventions targeting neuro-inflammation are important for improving outcomes in glioma patients.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Allergy
Veronika Kanderova, Tamara Svobodova, Simon Borna, Martina Fejtkova, Vendula Martinu, Jana Paderova, Michael Svaton, Jarmila Kralova, Eva Fronkova, Adam Klocperk, Stepanka Pruhova, Min Ae Lee-Kirsch, Ludmila Hornofova, Miroslav Koblizek, Petr Novak, Olga Zimmermannova, Zuzana Parackova, Anna Sediva, Tomas Kalina, Ales Janda, Jana Kayserova, Marcela Dvorakova, Milan Macek, Petr Pohunek, Petr Sedlacek, Ashleigh Poh, Matthias Ernst, Tomas Brdicka, Ondrej Hrusak, Jan Lebl
Summary: This article reports a new monogenic autoinflammatory disorder caused by a de novo activating mutation in the HCK gene, characterized by cutaneous vasculitis and chronic pulmonary inflammation. The study shows the aberrant functions of mutant HCK and the therapeutic efficacy of the Janus kinase 1/2 inhibitor Ruxolitinib in treating inflammatory lung disease.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2022)
Article
Hematology
Martina Fejtkova, Martina Sukova, Katerina Hlozkova, Karolina Skvarova Kramarzova, Marketa Rackova, David Jakubec, Marina Bakardjieva, Marketa Bloomfield, Adam Klocperk, Zuzana Parackova, Anna Sediva, Jahnavi Aluri, Michaela Novakova, Tomas Kalina, Eva Fronkova, Ondrej Hrusak, Hana Malcova, Petr Sedlacek, Zuzana Liba, Martin Kudr, Jan Stary, Megan A. Cooper, Michael Svaton, Veronika Kanderova
Summary: Our study identified a novel mutation c.1715G>T (p.G572V) in the Toll-like receptor 8 (TLR8) gene, which causes an autoimmune and autoinflammatory disorder in a family with monozygotic male twins. In vitro assays confirmed the pathogenicity of the mutation and revealed increased inflammatory responses.
AMERICAN JOURNAL OF HEMATOLOGY
(2022)
Letter
Immunology
Marketa Bloomfield, Zuzana Parackova, Jana Hanzlikova, Jan Lastovicka, Anna Sediva
JOURNAL OF CLINICAL IMMUNOLOGY
(2022)
Article
Immunology
Adam Klocperk, David Friedmann, Alexandra Emilia Schlaak, Susanne Unger, Zuzana Parackova, Sigune Goldacker, Anna Sediva, Bertram Bengsch, Klaus Warnatz
Summary: By analyzing CD8 T cell homeostasis in patients with CVID, it was found that these cells undergo advanced differentiation, exhaustion, activation, and immunoregulatory processes. Assessing the phenotype of CD8 T cells can help predict the risk of CVID patients and provide a better understanding of the pathogenesis of CVID, including T cell exhaustion and regulation mechanisms.
JOURNAL OF CLINICAL IMMUNOLOGY
(2022)
Article
Immunology
Jagoda Mierzejewska, Katarzyna Wegierek-Ciura, Joanna Rossowska, Agnieszka Szczygiel, Natalia Anger-Gora, Bozena Szermer-Olearnik, Magdalena Geneja, Elzbieta Pajtasz-Piasecka
Summary: The purpose of this study was to investigate the effect of dendritic cell (DC) transduction with lentiviral vectors carrying IL-18 and/or IL-12 genes on antitumor activity in vitro and in vivo. The results showed that genetically modified DCs producing IL-12 and/or IL-18 enhanced the antitumor response and triggered a systemic immune response against the tumor.
JOURNAL OF IMMUNOLOGY RESEARCH
(2022)
Article
Pharmacology & Pharmacy
Reynald Thinard, Attila E. Farkas, Marta Halasa, Melanie Chevalier, Klaudia Brodaczewska, Aleksandra Majewska, Robert Zdanowski, Maria Paprocka, Joanna Rossowska, Lam Tri Duc, Ruth Greferath, Istvan Krizbai, Fred Van Leuven, Claudine Kieda, Claude Nicolau
Summary: This study developed a novel approach to facilitate the penetration of antibody fragments into the brain parenchyma by leveraging the homing properties of endothelial progenitor cells. The results showed that the production and secretion of antibody fragments at the blood-brain barrier level could lead to their migration to the brain parenchyma where they might exert a therapeutic effect.
Article
Immunology
Marketa Bloomfield, Irena Zentsova, Tomas Milota, Anna Sediva, Zuzana Parackova
Summary: In this article, the characteristics and functional abnormalities of monocytes in patients with STAT1 gain-of-function mutations are studied. The study found that these monocytes exhibit proinflammatory phenotypes and an inflammatory skew in their cytokine secretion profile, with enhanced responsiveness to TLR7/8 stimulation. These features may be associated with autoimmune diseases related to STAT1 gain-of-function mutations.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Medicine, General & Internal
Zuzana Parackova, Irena Zentsova, Hana Malcova, Dita Cebecauerova, Anna Sediva, Rudolf Horvath
Summary: This study found that posttranslational modifications (PTMs) of proteins and dysregulated generation of neutrophil extracellular traps (NETs) contribute to the pathogenesis of juvenile idiopathic arthritis (JIA) by inducing the generation of autoantibodies. These findings suggest that regulating inflammation using immune therapy may help prevent the development of autoimmune responses.
FRONTIERS IN MEDICINE
(2022)
Article
Immunology
Zuzana Parackova, Irena Zentsova, Petra Vrabcova, Anna Sediva, Marketa Bloomfield
Summary: STAT1 GOF mutations are responsible for chronic mucocutaneous candidiasis (CMC) and autoimmune manifestations. Our study shows that these mutations affect the properties of dendritic cells (DCs) and alter their functions. The altered DCs lose their tolerogenic functions, become proinflammatory, and have decreased ability to induce Th17 cells. The results suggest that DCs play a direct role in the immune pathology associated with STAT1 GOF mutations.
CLINICAL IMMUNOLOGY
(2023)
Article
Allergy
Tomas Milota, Jitka Smetanova, Aneta Skotnicova, Michal Rataj, Jan Lastovicka, Hana Zelena, Zuzana Parackova, Martina Fejtkova, Veronika Kanderova, Eva Fronkova, Katerina Rejlova, Anna Sediva, Tomas Kalina
Summary: Patients with CVID showed measurable antibody and T-cell immune responses after receiving the BNT162b2 vaccine, but the antibody titers were low and decreased rapidly, while the T-cell response remained stable. The vaccine demonstrated favorable safety and clinical outcomes in preventing severe COVID-19.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE
(2023)
Article
Biochemistry & Molecular Biology
Julita Kulbacka, Anna Choromanska, Anna Szewczyk, Olga Michel, Dagmara Baczynska, Andrzej Sikora, Joanna Rossowska, Marek Kulbacki, Nina Rembialkowska
Summary: Ultrashort electric pulses in the nanosecond range can affect cell structures and functioning by altering calcium levels. This study examined the impact of nsPEFs combined with calcium on human colon adenocarcinoma cell lines. The results showed that nsPEF with calcium was cytotoxic for drug resistant cancer cells and safe for normal cells. The treatment also caused oxidative stress and altered cell morphology.
BIOELECTROCHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Patrycja Ledwon, Waldemar Goldeman, Katarzyna Haldys, Michal Jewginski, Greta Calamai, Joanna Rossowska, Anna Maria Papini, Paolo Rovero, Rafal Latajka
Summary: The development of skin-care products, including cosmeceuticals containing proven active ingredients, such as peptides, is on the rise. However, the applicability of whitening agents in these products is often limited due to drawbacks like toxicity and lack of stability. In this study, thiosemicarbazone (TSC)-peptide conjugates were found to inhibit diphenolase activity, and were tested as tyrosinase and melanogenesis inhibitors in B16F0 cells. The results showed that TSC1-conjugates had a lower IC50 value than the widely used reference compound kojic acid, making them potential candidates for tyrosinase inhibition.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Adriana A. de Jesus, Guibin Chen, Dan Yang, Tomas Brdicka, Natasha M. Ruth, David Bennin, Dita Cebecauerova, Hana Malcova, Helen Freeman, Neil Martin, Karel Svojgr, Murray H. Passo, Farzana Bhuyan, Sara Alehashemi, Andre T. Rastegar, Katsiaryna Uss, Lela Kardava, Bernadette Marrero, Iris Duric, Ebun Omoyinmi, Petra Peldova, Chyi-Chia Richard Lee, David E. Kleiner, Colleen M. Hadigan, Stephen M. Hewitt, Stefania Pittaluga, Carmelo Carmona-Rivera, Katherine R. Calvo, Nirali Shah, Miroslava Balascakova, Danielle L. Fink, Radana Kotalova, Zuzana Parackova, Lucie Peterkova, Daniela Kuzilkova, Vit Campr, Lucie Sramkova, Angelique Biancotto, Stephen R. Brooks, Cameron Manes, Eric Meffre, Rebecca L. Harper, Hyesun Kuehn, Mariana J. Kaplan, Paul Brogan, Sergio D. Rosenzweig, Melinda Merchant, Zuoming Deng, Anna Huttenlocher, Susan L. Moir, Douglas B. Kuhns, Manfred Boehm, Karolina Skvarova Kramarzova, Raphaela Goldbach-Mansky
Summary: Neutrophilic inflammation is a common feature in many genetic autoinflammatory diseases. This study presents three cases of newborns with perinatal-onset of neutrophilic cutaneous small vessel vasculitis and systemic inflammation, and identified novel variants in the Src-family tyrosine kinase LYN that lead to Lyn kinase activation. The research highlights the critical role of Lyn kinase in modulating inflammatory signals, regulating microvascular permeability, neutrophil recruitment, and promoting hepatic fibrosis.
NATURE COMMUNICATIONS
(2023)
Article
Immunology
Zuzana Parackova, Petra Vrabcova, Irena Zentsova, Anna Sediva, Marketa Bloomfield
Summary: STAT1 gain-of-function (GOF) mutations lead to an inborn error of immunity with a wide range of manifestations, including chronic mucocutaneous candidiasis (CMC) and non-infectious complications such as autoimmunity and vascular issues. This study focuses on the role of neutrophils in the immunodysregulation and vascular pathology associated with STAT1 GOF CMC. The results suggest that STAT1 GOF neutrophils exhibit immature and highly activated phenotypes, with increased propensity for degranulation, NETosis, and platelet-neutrophil aggregation.
JOURNAL OF CLINICAL IMMUNOLOGY
(2023)