Article
Multidisciplinary Sciences
Shunli Fu, Lili Chang, Shujun Liu, Tong Gao, Xiao Sang, Zipeng Zhang, Weiwei Mu, Xiaoqing Liu, Shuang Liang, Han Yang, Huizhen Yang, Qingping Ma, Yongjun Liu, Na Zhang
Summary: The authors developed a pH and photothermal therapy targeted nanoparticle that simultaneously targeted tumours and lymph nodes, leading to mobilization of anti-tumour cytotoxic T cells and NK cells and a synergistic therapeutic effect with immune checkpoint blockade. Targeting the immunosuppressive microenvironment of tumours is a critical strategy in immunotherapy and this study highlights the important role of the tumour lymph node immune microenvironment. Combining lymph node targeting with immune checkpoint blockade significantly enhances the effectiveness of T and NK cells and suppresses tumour growth.
NATURE COMMUNICATIONS
(2023)
Article
Microbiology
Yiping Wang, Nathan Ungerleider, Brett A. Hoffman, Mehmet Kara, Paul J. Farrell, Erik K. Flemington, Nara Lee, Scott A. Tibbetts
Summary: Oncogenic gammaherpesviruses employ various strategies to colonize the host, including the expression of noncoding RNAs (ncRNAs). The specific functions of EBV-encoded RNA 1 and 2 (EBER1 and EBER2) have remained largely unknown, despite extensive investigation. This study reveals that an EBV EBER2 variant highly associated with B cell lymphoma significantly promotes expansion of the infected B cell pool in vivo, coinciding with altered B cell differentiation.
Review
Biochemistry & Molecular Biology
Oriol de Barrios, Maribel Parra
Summary: BCP-ALL is a highly aggressive malignancy with worse prognosis in infants. Genetic signatures and epigenetic alterations play a role in leukemogenesis, with DNA methylation patterns and histone modifications impacting oncogene activation. An integrated understanding of epigenetic disorders is crucial for improving therapeutic options and disease prognosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Xiang Zhang, Patrick Schuhmachers, Andre Mourao, Piero Giansanti, Anita Murer, Sybille Thumann, Cornelia Kuklik-Roos, Sophie Beer, Stefanie M. Hauck, Wolfgang Hammerschmidt, Ralf Kueppers, Bernhard Kuster, Monika Raab, Klaus Strebhardt, Michael Sattler, Christian Muenz, Bettina Kempkes
Summary: This study demonstrates that the mitotic polo-like kinase 1 (PLK1) binds to EBNA2, phosphorylates its transactivation domain, and thereby inhibits its biological activity, ultimately reducing the risk of tumor development in healthy hosts infected with EBV.
Article
Virology
Diana A. Dominguez-Martinez, Jose I. Fontes-Lemus, Alejandro Garcia-Regalado, Angel Juarez-Flores, Ezequiel M. Fuentes-Panana
Summary: Helicobacter pylori and EBV are major risk factors for gastric cancer, and both can establish persistent infections and are considered carcinogenic. The study suggests that Helicobacter pylori infection facilitates the chemoattraction of EBV-infected B lymphocytes to the gastric mucosa, with IL-8 being identified as a powerful chemoattractant and CXCR2 as the main IL-8 receptor induced by EBV. Inhibition of IL-8 and CXCR2 reduces the chemoattraction of EBV-infected B lymphocytes, indicating an interaction mechanism between Helicobacter pylori and EBV.
Article
Multidisciplinary Sciences
Marloes I. I. Hofstee, Alper Cevirgel, Mary-Lene de Zeeuw-Brouwer, Lia de Rond, Fiona van der Klis, Anne-Marie Buisman
Summary: This study found that infection with CMV and EBV can alter the numbers and composition of immune cells in individuals of different age groups, with more significant effects observed in older adults and those with obesity.
SCIENTIFIC REPORTS
(2023)
Article
Cell Biology
Luc Gailhouste, Masayuki Sudoh, Xian-Yang Qin, Koichi Watashi, Takaji Wakita, Takahiro Ochiya, Tomokazu Matsuura, Soichi Kojima, Yutaka Furutani
Summary: Chronic hepatitis B virus (HBV) infections affect approximately 250 million people worldwide and current interferon-alpha (IFN alpha) therapies have unsatisfactory cure rates, necessitating the development of alternative therapeutic molecules. This study demonstrates that epigenetic reprogramming can enhance the IFN alpha response in HBV-infected cells, showing potential for screening IFN-like compounds in cell-based experiments.
CELL DEATH DISCOVERY
(2021)
Article
Oncology
Francesca Manara, Antonin Jay, Grace Akinyi Odongo, Fabrice Mure, Mohamed Ali Maroui, Audrey Diederichs, Cecilia Sirand, Cyrille Cuenin, Massimo Granai, Lucia Mundo, Hector Hernandez-Vargas, Stefano Lazzi, Rita Khoueiry, Henri Gruffat, Zdenko Herceg, Rosita Accardi
Summary: Endemic Burkitt lymphoma is a pediatric cancer caused by EBV infection, malaria, and environmental carcinogens. This study identified a common molecular signature associated with both EBV and AFB1 exposure, which may play a crucial role in the development of lymphoma.
Article
Oncology
Aneta Ledererova, Lenka Dostalova, Veronika Kozlova, Helena Peschelova, Adriana Ladungova, Martin Culen, Tomas Loja, Jan Verner, Sarka Pospisilova, Michal Smida, Veronika Mancikova
Summary: The study explores the mechanism of antigen loss in B-cell tumors relapse to CART-19, finding that the lack of CD19 expression is caused by promoter DNA hypermethylation. This epigenetically driven antigen escape can be partially reversible by treatment with a demethylating agent, representing a novel escape mechanism for CD19 loss in B-cell tumors.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Multidisciplinary Sciences
Cecilia Fahlquist-Hagert, Thomas R. Wittenborn, Ewa Terczynska-Dyla, Kristian Savstrup Kastberg, Emily Yang, Alysa Nicole Rallistan, Quinton Raymond Markett, Gudrun Winther, Sofie Fonager, Lasse F. Voss, Mathias K. Pedersen, Nina van Campen, Alexey Ferapontov, Lisbeth Jensen, Jinrong Huang, John D. Nieland, Cees E. van der Poel, Johan Palmfeldt, Michael C. Carroll, Paul J. Utz, Yonglun Luo, Lin Lin, Soren E. Degn
Summary: Circumstantial evidence suggests that B cells may instruct T cells to break tolerance. A murine model experiment demonstrated that the autoimmune response can be initiated outside of germinal centers. B cells can directly relay autoreactivity between different compartments of MHC-restricted T cells and propagate the autoimmune response.
NATURE COMMUNICATIONS
(2023)
Article
Gastroenterology & Hepatology
Chao Zhang, Jiesheng Li, Yongqian Cheng, Fanping Meng, Jin-Wen Song, Xing Fan, Hongtao Fan, Jing Li, Yu-Long Fu, Ming-Ju Zhou, Wei Hu, Si-Yu Wang, Yuan-Jie Fu, Ji-Yuan Zhang, Ruo-Nan Xu, Ming Shi, Xueda Hu, Zemin Zhang, Xianwen Ren, Fu-Sheng Wang
Summary: In this study, the comprehensive immune responses in different phases of HBV infection were analyzed using single-cell RNA sequencing. The results showed that both immune active and acute recovery phases were characterized by high levels of exhausted CD8+ T cells in the liver. Significant cell-cell interactions were observed between these exhausted T cells and regulatory CD4+ T cells, as well as between T cells and macrophages. Specific subsets of CD8+ T cells were expanded during the acute recovery phase, providing a potential marker for viral resolution. This study provides important insights into the immunopathogenesis of HBV and the development of effective therapeutic strategies.
Article
Medicine, Research & Experimental
Yeon Joo Kim, Katherine M. Sheu, Jennifer Tsoi, Gabriel Abril-Rodriguez, Egmidio Medina, Catherine S. Grasso, Davis Y. Torrejon, Ameya S. Champhekar, Kevin Litchfield, Charles Swanton, Daniel E. Speiser, Philip O. Scumpia, Alexander Hoffmann, Thomas G. Graeber, Cristina Puig-Saus, Antoni Ribas
Summary: The process of melanoma dedifferentiation in response to anti-PD-1 therapy challenges the traditional view that neural crest dedifferentiation is entirely negative, as it corresponded with improved outcomes in patients. This suggests that treatment-induced dedifferentiation may have beneficial effects in melanoma, despite initially appearing counterintuitive. In vitro studies also demonstrated that exposure to IFN-gamma led to changes in chromatin landscape, resulting in a neural crest dedifferentiation signature in melanoma cell lines.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Review
Immunology
Nicolas Jacquelot, Cyril Seillet, Eric Vivier, Gabrielle T. Belz
Summary: Innate lymphoid cells (ILCs) play a role in immune responses and have been found to have pleiotropic effects in various tissues, including both tissue repair and immunopathology toward allergens and promotion of tumorigenesis. Recent studies suggest that non-NK ILCs might be harnessed for anti-tumor responses. Gabrielle Belz and colleagues review the influence of ILCs on cancer immune responses.
Article
Multidisciplinary Sciences
Javier Rodriguez-Ubreva, Anna Arutyunyan, Marc Jan Bonder, Lucia Del Pino-Molina, Stephen J. Clark, Carlos de la Calle-Fabregat, Luz Garcia-Alonso, Louis-Francois Handfield, Laura Ciudad, Eduardo Andres-Leon, Felix Krueger, Francesc Catala-Moll, Virginia C. Rodriguez-Cortez, Krzysztof Polanski, Lira Mamanova, Stijn van Dongen, Vladimir Yu Kiselev, Maria T. Martinez-Saavedra, Holger Heyn, Javier Martin, Klaus Warnatz, Eduardo Lopez-Granados, Carlos Rodriguez-Gallego, Oliver Stegle, Gavin Kelsey, Roser Vento-Tormo, Esteban Ballestar
Summary: In this study, single-cell omics analyses were performed in CVID-discordant monozygotic twins, revealing epigenetic and transcriptional alterations associated with activation in memory B cells. These findings provide valuable insights into the diagnosis and treatment of CVID patients.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Michela Consonni, Claudio Garavaglia, Andrea Grilli, Claudia de Lalla, Alessandra Mancino, Lucia Mori, Gennaro De Libero, Daniela Montagna, Monica Casucci, Marta Serafini, Chiara Bonini, Daniel Haussinger, Fabio Ciceri, Massimo Bernardi, Sara Mastaglio, Silvio Bicciato, Paolo Dellabona, Giulia Casorati
Summary: The study demonstrates that engineered human T cells can effectively target leukemia cells expressing CD1c through a specific mLPA-TCR, delaying leukemia progression in mouse models. This approach has the potential to overcome MHC barriers between different donors and recipients, reducing the risk of graft-versus-host disease.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Jayaraju Dheekollu, Andreas Wiedmer, Kasirajan Ayyanathan, Julianna S. Deakyne, Troy E. Messick, Paul M. Lieberman
Summary: This study reveals that EBNA1 forms cell cycle-dependent DNA crosslinks with the EBV origin of plasmid replication and the tyrosine 518 residue is essential for this process. These crosslinks and single-strand cleavage are critical for replication termination and viral episome maintenance.
Article
Microbiology
R. Jason Lamontagne, Samantha S. Soldan, Chenhe Su, Andreas Wiedmer, Kyoung Jae Won, Fang Lu, Aaron R. Goldman, Jayamanna Wickramasinghe, Hsin-Yao Tang, David W. Speicher, Louise Showe, Andrew V. Kossenkov, Paul M. Lieberman
Summary: EBV immortalizes resting B-lymphocytes through orchestrated reprogramming of chromatin structure, transcription, and metabolism. The virus alters accessible chromatin, leading to complex transcriptional responses and changes in nucleotide metabolism. Purine metabolism, particularly the role of adenosine deaminase, emerges as a major therapeutic target in EBV-driven lymphoid cancers. This study highlights the importance of purine metabolism and ADA in EBV-induced immortalization process.
Article
Oncology
Samantha S. Soldan, Emma M. Anderson, Drew M. Frase, Yue Zhang, Lisa B. Caruso, Yin Wang, Julianna S. Deakyne, Benjamin E. Gewurz, Italo Tempera, Paul M. Lieberman, Troy E. Messick
Summary: The study demonstrated that the EBNA1 inhibitor VK-1727 selectively inhibited cell growth in EBV-positive gastric carcinoma and reduced tumor growth in animal models, but not in EBV-negative gastric carcinoma. Short-term treatment tended to activate viral genes, while long-term treatment resulted in significant decrease in viral gene expression.
Article
Microbiology
Ian Tietjen, Joel Cassel, Emery T. Register, Xiang Yang Zhou, Troy E. Messick, Frederick Keeney, Lily D. Lu, Karren D. Beattie, Topul Rali, Pablo Tebas, Hildegund C. J. Ertl, Joseph M. Salvino, Rohan A. Davis, Luis J. Montaner
Summary: The study identified (-)-hopeaphenol as a potent inhibitor of SARS-CoV-2 cell entry and replication, showing activity against different variants of the virus. This compound has potential as an antiviral agent in combating the COVID-19 pandemic.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Microbiology
Chenhe Su, Fang Lu, Samantha S. Soldan, R. Jason Lamontagne, Hsin-Yao Tang, Giorgia Napoletani, Paul J. Farrell, Italo Tempera, Andrew V. Kossenkov, Paul M. Lieberman
Summary: The study reveals a new transcriptional mechanism by which EBV encoded EBNA2 down-regulates HLA class II gene expression, impacting T-cell recognition of infected cells. EBNA2 competes with CIITA binding, leading to CIITA transcriptional down-regulation and subsequent HLA-II gene expression attenuation. This indirect regulation is proposed to be due to enhancer competition at neighboring chromosome domains.
Article
Medicine, General & Internal
Jared M. Andrews, Sarah C. Pyfrom, Jennifer A. Schmidt, Olivia I. Koues, Rodney A. Kowalewski, Nicholas R. Grams, Jessica J. Sun, Leigh R. Berman, Eric J. Duncavage, Yi-Shan Lee, Amanda F. Cashen, Eugene M. Oltz, Jacqueline E. Payton
Summary: This study mapped the transcriptional circuitry of the most common blood cancers, revealing that a critical subset of B-cell transcription factors and their cognate enhancers form self-regulatory transcriptional feedback loops, representing a shared mechanism underlying diverse subtypes of B-cell lymphoma.
Review
Microbiology
Samantha S. Soldan, Paul M. Lieberman
Summary: EBV plays a significant role in the development of multiple sclerosis (MS) through the reprogramming of infected B lymphocytes and the chronic presentation of viral antigens. Understanding how EBV contributes to MS may also provide insights into the relationship between EBV and cancer.
NATURE REVIEWS MICROBIOLOGY
(2023)
Article
Virology
Yang Mei, Troy E. Messick, Jayaraju Dheekollu, Hee Jong Kim, Sudheer Molugu, Leonardo Josue Castro Munoz, Vera Moiskeenkova-Bell, Kenji Murakami, Paul M. Lieberman
Summary: EBV latent infection is associated with various diseases. EBNA1 is a viral protein that plays a crucial role in maintaining the virus during latent infection. In this study, the structure of EBNA1 DNA-binding domain (DBD) and its interaction with different sites were determined using cryo-EM. The N-terminal domain (NTD) of EBNA1 was also found to interact with specific DNA sequences. These findings provide insights into the mechanisms of EBNA1 binding and may have implications for targeting EBNA1 in EBV-associated diseases.
JOURNAL OF VIROLOGY
(2022)
Article
Virology
Samantha S. Soldan, Troy E. Messick, Paul M. Lieberman
CURRENT OPINION IN VIROLOGY
(2022)
Article
Multidisciplinary Sciences
Matthew Charman, Nicholas Grams, Namrata Kumar, Edwin Halko, Joseph M. Dybas, Amber Abbott, Krystal K. Lum, Daniel Blumenthal, Elene Tsopurashvili, Matthew D. Weitzman
Summary: Biomolecular condensates formed by phase separation can compartmentalize and regulate cellular processes. Evidence suggests that membraneless subcellular compartments in virus-infected cells also form by phase separation. Here we demonstrate that phase separation of the human adenovirus 52-kDa protein plays a critical role in the coordinated assembly of infectious progeny particles. Our findings identify essential requirements for coordinated assembly of progeny particles and demonstrate that phase separation of a viral protein is critical for production of infectious progeny during adenovirus infection.
Article
Hematology
Zhiwei Ang, Luca Paruzzo, Katharina E. Hayer, Carolin Schmidt, Manuel Torres Diz, Feng Xu, Urvi Zankharia, Yunlin Zhang, Samantha Soldan, Sisi Zheng, Catherine D. Falkenstein, Joseph P. Loftus, Scarlett Y. Yang, Mukta Asnani, Patricia King Sainos, Vinodh Pillai, Emeline Chong, Marilyn M. Li, Sarah K. Tasian, Yoseph Barash, Paul M. Lieberman, Marco Ruella, Stephen J. Schuster, Andrei Thomas-Tikhonenko
Summary: Skipping of coding exons in CD19 and CD22 genes compromises immunotherapy response in B-cell malignancies. This study demonstrates that CD20 gene (MS4A1) also produces multiple mRNA isoforms with distinct untranslated regions. Modulating CD20 isoforms enhances CD20 expression and antibody-mediated cytotoxicity, potentially overcoming immunotherapy resistance.
Review
Microbiology
Samantha S. Soldan, Paul M. Lieberman
Summary: This review article examines the evidence for EBV as a causal agent of MS and discusses how various risk factors can affect EBV infection and immune control. The article focuses on the reprogramming of latently infected B lymphocytes by EBV and the chronic presentation of viral antigens as a potential mechanism for MS development. The potential for therapies targeting EBV to treat MS is also discussed.
NATURE REVIEWS MICROBIOLOGY
(2023)