Article
Multidisciplinary Sciences
Jeremy Poulet-Benedetti, Caroline Tonnerre-Doncarli, Anne-Laure Valton, Marc Laurent, Marie Gerard, Natalja Barinova, Nikolaos Parisis, Florian Massip, Franck Picard, Marie-Noelle Prioleau
Summary: In this study, the involvement of three elements (guanine-rich motifs potentially forming G-quadruplexes, nucleosome-free regions, and the histone variant H2A.Z) in the firing of replication origins in vertebrates were investigated. It was found that two guanine-rich motifs on the same DNA strand were sufficient to assemble a functional replication origin without inducing transcription. The guanine-rich motifs were associated with the formation of nucleosome-free regions and enrichment of H2A.Z. These findings suggest the importance of guanine-rich motifs in the organization and duplication of vertebrate genomes.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Dante S. Bortone, Mark G. Woodcock, Joel S. Parker, Benjamin G. Vincent
Summary: T-cell receptor (TCR) repertoire profiling is important in cancer immunology and immunotherapy, with diversity being a key statistic. A study found undersampling to be a major source of bias in diversity estimates, and a model was developed to improve the accuracy of diversity estimates, which could enhance predictions of patient responses to immunotherapy.
CANCER IMMUNOLOGY RESEARCH
(2021)
Review
Dermatology
Axel A. Almet, Hao Yuan, Karl Annusver, Raul Ramos, Yingzi Liu, Julie Wiedemann, Dara H. Sorkin, Ning Xu Landen, Eniko Sonkoly, Muzlifah Haniffa, Qing Nie, Beate M. Lichtenberger, Malte D. Luecken, Bogi Andersen, Lam C. Tsoi, Fiona M. Watt, Johann E. Gudjonsson, Maksim Plikus, Maria Kasper
Summary: Single-cell technologies are crucial in both basic and translational research in dermatology, but a central reference atlas for normal human skin is still lacking. As part of the Human Cell Atlas project, a Skin Biological Network has been established to build a consensus Human Skin Cell Atlas. The goals for Atlas 1.0 are discussed and it is expected to uncover new aspects of skin biology.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2023)
Article
Cell Biology
Gaoxingyu Huang, Xiechao Zhan, Chao Zeng, Xuechen Zhu, Ke Liang, Yanyu Zhao, Pan Wang, Qifan Wang, Qiang Zhou, Qinghua Tao, Minhao Liu, Jianlin Lei, Chuangye Yan, Yigong Shi
Summary: The structure of the nuclear ring subunit of the nuclear pore complex (NPC) is reported in this study. The nuclear ring subunit consists of two Y complexes, each with nucleoporin ELYS closely associated with Nup160 and Nup37. Unlike other ring subunits, the nuclear ring subunit contains only one molecule each of Nup205 and Nup93. A composite atomic model of the central ring scaffold is generated, facilitating functional understanding of vertebrate NPC.
Article
Oncology
Hongwen Li, Jing Li, Jiazhuo Wu, Zhuangzhuang Shi, Yuyang Gao, Wenting Song, Jiwei Li, Zhaoming Li, Mingzhi Zhang
Summary: In this study, a second-generation CAR construct targeting CD38 molecule was developed and CAR-T cells showed higher cytotoxicity to MM cell lines and primary MM cells than control T cells in vitro. CAR-T cells also exhibited enhanced cytotoxicity against primary MM cells and showed significant antitumor effect on xenograft mice models in vivo.
Article
Biology
Derek M. Britain, Jason P. Town, Orion David Weiner
Summary: This study uncovers the location where kinetic proofreading is executed in the signaling cascade, showing a progressive increase in the strength of kinetic proofreading from Zap70 recruitment to downstream DAG generation. The findings suggest a distributed mechanism of kinetic proofreading, with proofreading steps occurring both at the receptor and at slower resetting downstream signaling complexes, which may help balance antigen sensitivity and discrimination.
Article
Multidisciplinary Sciences
Gabriel K. Griffin, Jingyi Wu, Arvin Iracheta-Vellve, James C. Patti, Jeffrey Hsu, Thomas Davis, Deborah Dele-Oni, Peter P. Du, Aya G. Halawi, Jeffrey J. Ishizuka, Sarah Y. Kim, Susan Klaeger, Nelson H. Knudsen, Brian C. Miller, Tung H. Nguyen, Kira E. Olander, Malvina Papanastasiou, Suzanna Rachimi, Emily J. Robitschek, Emily M. Schneider, Mitchell D. Yeary, Margaret D. Zimmer, Jacob D. Jaffe, Steven A. Carr, John G. Doench, W. Nicholas Haining, Kathleen B. Yates, Robert T. Manguso, Bradley E. Bernstein
Summary: A CRISPR-Cas9 screen in mouse tumour models treated with immune checkpoint blockade identified SETDB1 as an epigenetic checkpoint protein that suppresses tumour-intrinsic immunogenicity. Loss of SETDB1 leads to derepression of immune-stimulating genes and triggers TE-specific cytotoxic T cell responses, suggesting it as a potential target for immunotherapy in cancer treatment.
Review
Immunology
Ya-Ting Qin, Ya-Ping Li, Xi-Wen He, Xi Wang, Wen-You Li, Yu-Kui Zhang
Summary: Chimeric antigen receptor-T (CAR-T) cell therapy is facing challenges due to complex manufacturing processes, high costs, and disappointing results in treating solid tumors. However, the fusion of immunology, cell biology, and biomaterials has provided new strategies to overcome these obstacles. Biomaterials-assisted CAR-T engineering has improved therapeutic efficacy and minimized side effects, offering a sustainable approach for cancer immunotherapy. This review summarizes the role of biomaterials in gene delivery for CAR-T cell generation and highlights their potential in synergistic immunotherapy for solid tumors.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Gastroenterology & Hepatology
Christoph Schultheiss, Donjete Simnica, Edith Willscher, Anna Oberle, Lorenzo Fanchi, Nicola Bonzanni, Nils H. Wildner, Julian Schulze Zur Wiesch, Christina Weiler-Normann, Ansgar W. Lohse, Mascha Binder
Summary: Patients with autoimmune hepatitis exhibit significant and persistent T-cell architectural changes, which may explain the high relapse rates after tapering immunosuppression. Liver T-cell clusters shared between patients may mediate liver damage and require further study.
Article
Biochemistry & Molecular Biology
Vahid Yekehfallah, Saghar Pahlavanneshan, Ali Sayadmanesh, Zahra Momtahan, Bin Ma, Mohsen Basiri
Summary: Chimeric antigen receptor (CAR) T-cell therapy has shown promising results in treating hematopoietic malignancies. However, the lack of specific tumor antigens with low expression in healthy cells is a challenge in solid tumors. This study constructed and evaluated CAR T cells targeting placental alkaline phosphatase (PLAP) antigen, showing that PLAP CAR T cells not only proliferated but also eliminated cancer cells in vitro. Increased secretion of IL-2, granzyme A, and IFN-gamma was observed in PLAP CAR T cells upon exposure to target cells. PLAP CAR T cells are potential candidates for further investigation in cervical cancer and other solid tumors.
Article
Biochemistry & Molecular Biology
Amanda Souza Camara, Martin Mascher
Summary: The organisation of chromatin is crucial for cellular functions, but the mechanisms behind the formation of different chromatin regions are not yet well understood. Polymer models have been used to study these mechanisms, but further research is needed to consolidate the models.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Article
Multidisciplinary Sciences
Jonathan Green, Carissa A. Bruno, Lisa Traunmuller, Jennifer Ding, Sinisa Hrvatin, Daniel E. Wilson, Thomas Khodadad, Jonathan Samuels, Michael E. Greenberg, Christopher D. Harvey
Summary: A subset of somatostatin inhibitory neurons in the posterior parietal cortex provides a cell-type-specific error-correction signal through self-excitation circuit motif for goal-directed navigation.
Article
Biochemistry & Molecular Biology
Kento Fujiwara, Masaki Kitaura, Ayaka Tsunei, Hotaka Kusabuka, Erika Ogaki, Naoki Okada
Summary: Genetically engineered T cells expressing CAR have potential to eliminate tumor cells but may cause severe side effects. Optimization of CAR structure and signaling can improve efficacy and toxicity of CAR-T cells. The study highlights the importance of CAR structure and signaling on CAR-T cell function.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Oncology
Siwei Deng, Yuliang Feng, Siim Pauklin
Summary: This review discusses the importance of three-dimensional chromatin structures in biological processes and diseases, as well as the key structural protein elements involved in chromatin interactions. The recent development of technologies and bioinformatics approaches for studying chromatin interactions in gene expression regulation is also summarized.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2022)
Article
Cell Biology
Tom Pieper, Kristian Daniel Ralph Roth, Viktor Glaser, Tobias Riet, Laura Elisa Buitrago-Molina, Maike Hagedorn, Maren Lieber, Michael Hust, Fatih Noyan, Elmar Jaeckel, Matthias Hardtke-Wolenski
Summary: Adoptive transfer of antigen-specific regulatory T cells (Tregs) has shown promising results in treating autoimmune diseases. However, obtaining sufficient antigen-specific Tregs from patients with autoimmune disorders remains challenging. In this study, researchers aimed to generate CARs against TSPAN7, a membrane protein highly expressed on the surface of pancreatic beta cells, using phage display technology. Although the resulting CARs were functional and specifically activated by the target structure, they could not recognize TSPAN7 on the surface of beta cells. This study demonstrates the power of CAR technology in generating antigen-specific T cells and provides new approaches for functional CAR generation.
Article
Allergy
Veronique Bordas-Le Floch, Nathalie Berjont, Thierry Batard, Nirupama Varese, Robyn E. O'Hehir, Walter G. Canonica, Menno C. van Zelm, Laurent Mascarell
Summary: This study found that after house dust mite immunotherapy, there is a significant increase in HDM-specific serum IgG2 responses among high responders. Subjects benefiting the most from HDM-AIT show a higher correlation between HDM-specific IgG2, IgE, and/or IgG4 responses, which may help differentiate between high and low responders.
Editorial Material
Cell Biology
Gemma E. Hartley, Menno C. van Zelm, Marcus J. Robinson
IMMUNOLOGY AND CELL BIOLOGY
(2022)
Article
Allergy
Maud A. W. Hermans, Jorn J. Heeringa, Sigrid G. A. Swagemakers, Benjamin Schrijver, Paul L. A. van Daele, Peter J. van der Spek, P. Martin van Hagen, Menno C. van Zelm, Wim A. Dik
Summary: This study observed altered distribution of leukocyte subsets and a proinflammatory proteome in patients with indolent systemic mastocytosis (ISM). The researchers hypothesized that neoplastic mast cells might recruit and activate plasmacytoid dendritic cells, monocytes, and T cells, leading to a vicious cycle of inflammation.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2022)
Article
Immunology
Daniela Kuzilkova, Joan Punet-Ortiz, Pei M. Aui, Javier Fernandez, Karel Fiser, Pablo Engel, Menno C. van Zelm, Tomas Kalina
Summary: This study developed a flow cytometric procedure for standardized quantitative expression profiling of surface antigens on blood leukocyte subsets across multiple research laboratories. The designed tubes can discriminate 27 leukocyte subsets and detect the expression of PE-conjugated CD markers.
FRONTIERS IN IMMUNOLOGY
(2022)
Editorial Material
Immunology
Menno C. van Zelm
Summary: An analysis of memory B cell responses to the Spike antigen after Omicron BA.1 breakthrough infections suggests the presence of original antigenic sin.
SCIENCE IMMUNOLOGY
(2022)
Article
Oncology
Gishan Ratnayake, Simone Reinwald, Jack Edwards, Nicholas Wong, Di Yu, Rachel Ward, Robin Smith, Andrew Haydon, Pei M. Au, Menno C. van Zelm, Sashendra Senthi
Summary: This study analyzed peripheral blood immune cells of patients receiving combination SABR and ICI to detect the effect of treatment and identify potential biomarkers that predict outcome. The results showed changes in the immunophenotype of blood T cells after the combination of immunotherapy and SABR, with some shifts attributable to SABR. Importantly, a T-cell signature at baseline was identified that best predicted response.
RADIOTHERAPY AND ONCOLOGY
(2022)
Article
Allergy
Craig McKenzie, Nirupama Varese, Pei Mun Aui, Simone Reinwald, Bruce D. Wines, P. Mark Hogarth, Francis Thien, Mark Hew, Jennifer M. Rolland, Robyn E. O'Hehir, Menno C. van Zelm
Summary: Sublingual immunotherapy for grass pollen allergy can modify allergic rhinitis and increase allergen-specific IgG(4). This study found that SLIT induces two transcriptionally unique subsets of B memory cells, and the changes in surface-expressed proteins on these subsets can be used as early biomarkers for treatment effects.
Article
Clinical Neurology
Casper L. de Mol, Marvin M. van Luijn, Karim L. Kreft, Kirsten I. M. Looman, Menno C. van Zelm, Tonya White, Henriette A. Moll, Joost Smolders, Rinze F. Neuteboom
Summary: This study aimed to assess whether polygenic risk scores for MS are associated with changes in the blood B-cell compartment in children. The results showed that a naive B-cell-MS-PRS was significantly associated with lower naive B-cell numbers and higher frequencies and absolute numbers of memory B cells in children. The findings suggest that specific genetic risk variants may impact the composition of the blood B-cell compartment during childhood, potentially influencing MS pathophysiology later in life.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Letter
Allergy
Gemma E. Hartley, Emily S. J. Edwards, Nirupama Varese, Irene Boo, Pei M. Aui, Scott J. Bornheimer, P. Mark Hogarth, Heidi E. Drummer, Robyn E. O'Hehir, Menno C. van Zelm
Correction
Immunology
Bruce D. Wines, Liriye Kurtovic, Halina M. Trist, Sandra Esparon, Ester Lopez, Klasina Chappin, Li-Jin Chan, Francesca L. Mordant, Wen Shi Lee, Nicholas A. Gherardin, Sheila K. Patel, Gemma E. Hartley, Phillip Pymm, James P. Cooney, James G. Beeson, Dale I. Godfrey, Louise M. Burrell, Menno C. van Zelm, Adam K. Wheatley, Amy W. W. Chung, Wai-Hong Tham, Kanta Subbarao, Stephen J. Kent, P. Mark Hogarth
FRONTIERS IN IMMUNOLOGY
(2023)
Letter
Allergy
Nathalie Berjont, Veronique Bordas-Le Floch, Robyn E. O'Hehir, Walter G. Canonica, Menno C. van Zelm, Thierry Batard, Laurent Mascarell
Article
Allergy
Emily S. J. Edwards, Samar Ojaimi, James Ngui, Go Hun Seo, Jihye Kim, Sanjeev Chunilal, Deborah Yablonski, Robyn E. O'Hehir, Menno C. van Zelm
Summary: This study found that mutations in the LCP2 gene may lead to combined immunodeficiency and early-onset immune dysregulation. The authors investigated a patient with specific antibody deficiency, autoimmunity, and inflammatory bowel disease and identified compound heterozygous missense variants in the proline-rich repeat domain of the SLP76 protein.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2023)
Article
Immunology
Holly A. Fryer, Gemma E. Hartley, Emily S. J. Edwards, Nirupama Varese, Irene Boo, Scott J. Bornheimer, P. Mark Hogarth, Heidi E. Drummer, Robyn E. O'Hehir, Menno C. van Zelm
Summary: Following the COVID-19 pandemic, novel vaccines have successfully reduced severe disease and death. Despite lower antibody responses, adenoviral vector vaccines are nearly as effective as mRNA vaccines in providing protection against severe disease. This study evaluated the antibody and memory B cell responses elicited by the adenoviral vector vaccine ChAdOx1 (AstraZeneca), compared to the mRNA vaccine BNT162b2 (Pfizer-BioNTech), and found that ChAdOx1 induced immune memory that conferred effective protection against severe COVID-19.
JOURNAL OF CLINICAL IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Thierry Batard, Walter G. Canonica, Oliver Pfaar, Mohamed H. Shamji, Robyn E. O'Hehir, Menno C. van Zelm, Laurent Mascarell
Summary: Allergy to house dust mites (HDM) is a common respiratory disease that affects over 500 million people worldwide. The two main species of HDM, Dermatophagoides pteronyssinus and D. farinae, are major sources of indoor allergens that trigger allergic inflammation. While symptomatic drugs can help alleviate symptoms, allergen immunotherapy is the only curative treatment for IgE-mediated type I respiratory allergies. This article reviews recent advances in various routes of immunotherapy, with a focus on subcutaneous (SCIT) and sublingual (SLIT) immunotherapy, which have transformed allergic treatments by improving symptoms and quality of life for patients.
MOLECULAR IMMUNOLOGY
(2023)
Meeting Abstract
Medicine, General & Internal
Emily S. J. Edwards, Julian Bosco, Josh Chatelier, Go Hun Seo, Rin Khang, Pei M. Aui, Robyn E. O'Hehir, Menno C. van Zelm
INTERNAL MEDICINE JOURNAL
(2022)
