Article
Immunology
Blagoje Soskic, Louisa E. Jeffery, Alan Kennedy, David H. Gardner, Tie Zheng Hou, Neil Halliday, Cayman Williams, Daniel Janman, Behzad Rowshanravan, Gideon M. Hirschfield, David M. Sansom
Summary: The expression patterns and associated functions of CD80 and CD86 on activated T cells exhibit clear differences, with CD80(+) T cells showing characteristics of induced regulatory T cells and CD86 being preferentially expressed on INF-gamma producing cells with effector T cell characteristics.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Yunlong Zhao, Christine Caron, Ya-Yuan Chan, Calvin K. Lee, Xiaozhen Xu, Jibin Zhang, Takeya Masubuchi, Chuan Wu, Jack D. Bui, Enfu Hui
Summary: In this study, it was discovered that B7 ligands on CD8+ T cells interact with CD28 in a cis configuration at membrane invaginations of the immunological synapse, which is driven by phosphoinositide-3-kinase (PI3K) and sorting-nexin-9 (SNX9) mediated membrane remodeling. Cis-B7:CD28 interactions activate CD28 signaling through protein kinase C theta (PKCq), promoting CD8+ T cell survival, migration, and cytokine production.
Article
Oncology
Justin C. Boucher, Gongbo Li, Hiroshi Kotani, Maria L. Cabral, Dylan Morrissey, Sae Bom Lee, Kristen Spitler, Nolan J. Beatty, Estelle Cervantes, Bishwas Shrestha, Bin Yu, Aslamuzzaman Kazi, Xuefeng Wang, Said M. Sebti, Marco L. Davila
Summary: Mutating the CD28 endodomain of CAR T cells optimized costimulation, leading to improved function and survival rates, which lays the foundation for enhancing CAR T-cell therapies.
CANCER IMMUNOLOGY RESEARCH
(2021)
Article
Cell Biology
Masashi Watanabe, Sofia Celli, Farrah A. Alkhaleel, Richard J. Hodes
Summary: This study elucidates the mechanism by which antigen-presenting T cells acquire B7 molecules via CD28-dependent trogocytosis from other cells and provide critical B7 co-stimulation to developing iNKT cells in thymic T cell development.
Article
Biochemistry & Molecular Biology
Vivien Beziat, Franck Rapaport, Jiafen Hu, Matthias Titeux, Mathilde Bonnet des Claustres, Mathieu Bourgey, Heather Griffin, Elise Bandet, Cindy S. Ma, Roya Sherkat, Hassan Rokni-Zadeh, David M. Louis, Majid Changi-Ashtiani, Ottavia M. Delmonte, Toshiaki Fukushima, Tanwir Habib, Andrea Guennoun, Taushif Khan, Noemi Bender, Mahbuba Rahman, Fredegonde About, Rui Yang, Geetha Rao, Claire Rouzaud, Jingwei Li, Debra Shearer, Karla Balogh, Fatima Al Ali, Manar Ata, Soroosh Dabiri, Mana Momenilandi, Justine Nammour, Marie-Alexandra Alyanakian, Marianne Leruez-Ville, David Guenat, Marie Materna, Lea Marcot, Natasha Vladikine, Christine Soret, Hassan Vahidnezhad, Leila Youssefian, Amir Hossein Saeidian, Jouni Uitto, Emilie Catherinot, Shadi Sadat Navabi, Mohammed Zarhrate, David T. Woodley, Mohamed Jeljeli, Thomas Abraham, Serkan Belkaya, Lazaro Lorenzo, Jeremie Rosain, Mousa Bayat, Fanny Lanternier, Olivier Lortholary, Faramarz Zakavi, Philippe Gros, Gerard Orth, Laurent Abel, Jean-Luc Pretet, Sylvie Fraitag, Emmanuelle Jouanguy, Mark M. Davis, Stuart G. Tangye, Luigi D. Notarangelo, Nico Marr, Tim Waterboer, David Langlais, John Doorbar, Alain Hovnanian, Neil Christensen, Xavier Bossuyt, Mohammad Shahrooei, Jean-Laurent Casanova
Summary: The study investigated a patient with HPV-2-driven "tree-man" phenotype and two relatives with severe HPV4-driven warts, revealing the relationship between a CD28 variant and T cell responses. Findings suggest that T cell responses are important in controlling HPV infections.
Article
Dermatology
Johanna Strobl, Laura M. Gail, Laura Krecu, Shaista Madad, Lisa Kleissl, Luisa Unterluggauer, Anna Redl, Kveta Brazdilova, Simona Saluzzo, Philipp Wohlfarth, Hanna A. Knaus, Margit Mitterbauer, Werner Rabitsch, Muzlifah Haniffa, Georg Stary
Summary: In patients with acute cutaneous GvHD, there is an increased abundance of MNPs with anti-inflammatory and tissue-remodelling properties, specifically CD163+ tissue-resident macrophages. In chronic cutaneous GvHD, skin macrophages are repolarized to proinflammatory macrophages producing IFN-gamma.
BRITISH JOURNAL OF DERMATOLOGY
(2023)
Article
Immunology
Alan Kennedy, Erin Waters, Behzad Rowshanravan, Claudia Hinze, Cayman Williams, Daniel Janman, Thomas A. Fox, Claire Booth, Anne M. Pesenacker, Neil Halliday, Blagoje Soskic, Satdip Kaur, Omar S. Qureshi, Emma C. Morris, Shinji Ikemizu, Christopher Paluch, Jiandong Huo, Simon J. Davis, Emmanuel Boucrot, Lucy S. K. Walker, David M. Sansom
Summary: CD28 and CTLA-4 play important roles in regulating T cell immunity. The study found that CTLA-4 captures ligands through transendocytosis, and CD80 leads to ubiquitination and degradation of CTLA-4, while CD86 allows CTLA-4 to detach and recycle back to the cell surface. Clinically relevant mutations disrupt CD86 transendocytosis and are associated with autoimmune diseases.
Article
Multidisciplinary Sciences
Guillem Sanchez Sanchez, Maria Papadopoulou, Abdulkader Azouz, Yohannes Tafesse, Archita Mishra, Jerry K. Y. Chan, Yiping Fan, Isoline Verdebout, Silvana Porco, Frederick Libert, Florent Ginhoux, Bart Vandekerckhove, Stanislas Goriely, David Vermijlen
Summary: This study examines the development of gamma delta T cells in fetal and pediatric individuals using single cell RNA gene expression and gamma delta T cell receptor sequencing. The findings reveal that fetal gamma delta thymocytes exhibit a wave-like pattern of development, while pediatric thymus generates only a small subset of effector cells. The study provides insights into the distinct programming of gamma delta T cell immunity in humans.
NATURE COMMUNICATIONS
(2022)
Article
Medicine, General & Internal
Seon Mee Kang, Jun Choul Lee, Bon Jeong Ku
Summary: This study found that soluble sCD81 levels were elevated in individuals with type 2 diabetes, and changes in sCD81 were only observed during the OGTT in the DM group. Therefore, soluble sCD81 may serve as a new diagnostic marker for type 2 diabetes.
Article
Immunology
Maya Fedeli, Mirela Kuka, Annamaria Finardi, Francesca Albano, Valentina Vigano, Matteo Iannacone, Roberto Furlan, Paolo Dellabona, Giulia Casorati
Summary: miR-21 plays a crucial role in CD28-dependent costimulation pathways in T cells, decreasing the activation threshold and enhancing sensitivity to antigenic stimulation and survival, thereby broadening immune surveillance range. However, miR-21 may also lead to the unleashing of autoimmunity.
CLINICAL & TRANSLATIONAL IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Marianne Dolz, Marko Hasiuk, John D. Gagnon, Mara Kornete, Romina Marone, Glenn Bantug, Robin Kageyama, Christoph Hess, K. Mark Ansel, Denis Seyres, Julien Roux, Lukas T. Jeker
Summary: CD28 provides the prototypical costimulatory signal for T cell activation. miR-17 similar to 92, induced by T cell receptor stimulation and enhanced by CD28 costimulation, acts as a central mediator for T cell activation by dampening negative regulators.
Article
Multidisciplinary Sciences
John P. Gleeson, Namit Chaudhary, Katherine C. Fein, Rose Doerfler, Patricia Hredzak-Showalter, Kathryn A. Whitehead
Summary: Breast milk contains cells that are beneficial for infant development, but little is known about these cells. This study characterized the cells in mature breast milk from healthy donors and identified the main cell population as epithelial cells, with several subpopulations including previously unidentified ones. These findings provide insights into the potential applications of breast milk cells in maternal and infant medicine.
Article
Oncology
In-Young Jung, Robert L. Bartoszek, Andrew J. Rech, Sierra M. Collins, Soon-Keat Ooi, Erik F. Williams, Caitlin R. Hopkins, Vivek Narayan, Naomi B. Haas, Noelle V. Frey, Elizabeth O. Hexner, Donald L. Siegel, Gabriela Plesa, David L. Porter, Adrian Cantu, John K. Everett, Sonia Guedan, Shelley L. Berger, Frederic D. Bushman, Friederike Herbst, Joseph A. Friederike
Summary: CAR T cell therapy has shown potential in treating hematologic cancers but is limited in solid tumors. Chronic stimulation of CAR T cells propagates inhibitory type I interferon signaling, hindering antitumor function. Knocking out the EGR2 transcriptional regulator improves CAR T cell efficacy and blocks interferon-induced dysfunction. The gene signature of EGR2 is a biomarker for CAR T cell failure and patient survival. Modulating CAR T cell-intrinsic resistance is crucial for improving therapy outcomes.
Article
Immunology
Manuel Reithofer, Sandra Rosskopf, Judith Leitner, Claire Battin, Barbara Bohle, Peter Steinberger, Beatrice Jahn-Schmid
Summary: The translation highlights the different effects of costimulatory signals on human CD8 T-cell responses, with CD28 costimulation enhancing antigen-reactive CD8 T cells, 4-1BB costimulation inducing bystander proliferation, and CD27 signals enhancing antigen-specific CD8 T cell responses.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2021)
Article
Immunology
Casimiro Luca Gigliotti, Elena Boggio, Francesco Favero, Danny Incarnato, Claudio Santoro, Salvatore Oliviero, Jose Maria Rojo, Silvia Zucchelli, Francesca Persichetti, Gianluca Baldanzi, Umberto Dianzani, Davide Cora
Summary: ICOS and CD28 costimulatory signals play distinct roles in the activation of naive T cells by modulating different sets of immunological and immunometabolic genes.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Kelly L. Mooney, Debra K. Czerwinski, Tanaya Shree, Matthew J. Frank, Sarah Haebe, Brock A. Martin, Stefano Testa, Ronald Levy, Steven R. Long
Summary: This study is the largest describing the use of serial FNA sampling to harvest cellular material during immunotherapy clinical trials. The successful use of FNA sampling opens up significant opportunities for future investigations into the dynamic effects of investigational agents, whether they be immunotherapies or targeted therapies.
CANCER CYTOPATHOLOGY
(2022)
Article
Oncology
Wan Xing Hong, Idit Sagiv-Barfi, Debra K. Czerwinski, Adrienne Sallets, Ronald Levy
Summary: The combination of synthetic TLR9 ligand CpG and agnostic OX40 antibody can trigger systemic antitumor immune responses, eradicating metastatic disease. Applying this in situ immunotherapy in the neoadjuvant setting can improve survival and minimize adverse effects.
Article
Multidisciplinary Sciences
Liora M. Schultz, Debra K. Czerwinski, Ronald Levy, Shoshana Levy
Summary: This study investigates the effect of CD81 costimulation on CAR transduction, finding that it enhances naive T cell activation and results in a CAR T cell product enriched with naive-derived CART cells.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Immunology
Idit Sagiv-Barfi, Debra K. Czerwinski, Tanaya Shree, Julian J. K. Lohmeyer, Ronald Levy
Summary: Antitumor T cell responses play a crucial role in cancer immunotherapy, but other immune system components are also necessary for effective T cell responses. This study demonstrates that combining Toll-like receptor 9 agonist CpG and Fc-fused IL-12 protein can induce body-wide therapeutic responses in multiple cancer models. These responses depend not only on T cells but also on B cells, which are activated by the treatment and required for optimal T cell activation. The addition of an agonistic antibody against OX40 further enhances T cell activation and therapeutic responses. These findings suggest the potential success of the combination of CpG, anti-OX40, and IL-12Fc in cancer patients and highlight the importance of B and T cell collaboration in this combination immunotherapy.
SCIENCE IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Stefano Testa, Ole A. W. Haabeth, Timothy R. Blake, Trevor J. Del Castillo, Debra K. Czerwinski, Ranjani Rajapaksa, Paul A. Wender, Robert M. Waymouth, Ronald Levy
Summary: Charge-altering releasable transporters (CARTs) containing fingolimod were synthesized to enhance mRNA delivery and expression in lymphocytes through ligand-receptor interaction. The fingolimod-conjugated CARTs showed superior transfection of activated T and B lymphocytes in vitro and increased mRNA delivery to specific cell populations in the spleen in vivo.
Article
Oncology
Michael Mentz, William Keay, Carolin Dorothea Strobl, Martina Antoniolli, Louisa Adolph, Michael Heide, Axel Lechner, Sarah Haebe, Elisa Osterode, Robert Kridel, Christoph Ziegenhain, Lucas Esteban Wange, Johannes Adrian Hildebrand, Tanaya Shree, Elisabeth Silkenstedt, Annette M. Staiger, German Ott, Heike Horn, Monika Szczepanowski, Julia Richter, Ronald Levy, Andreas Rosenwald, Wolfgang Enard, Ursula Zimber-Strobl, Michael Von Bergwelt-Baildon, Wolfgang Hiddemann, Wolfram Klapper, Marc Schmidt-Supprian, Martina Rudelius, Deepak Bararia, Verena Passerini, Oliver Weigert
Summary: The clinical course of follicular lymphoma (FL) is influenced by the molecular heterogeneity of tumor cells and interactions within the tumor microenvironment (TME). In this study, we found STAT6 mutations in 13% of FL cases, which enhanced the response of FL cells to IL-4 and were associated with increased expression of target genes and nuclear accumulation of pSTAT6. We identified PARP14 as a potential therapeutic target in STAT6-mutated FL cells, as its expression was upregulated and it played a role in the regulatory circuit.
Meeting Abstract
Hematology
Tanaya Shree, Sarah Haebe, Debra K. Czerwinski, Erik Eckhert, Grady Day, Anuja Sathe, Susan M. Grimes, Matthew J. Frank, Lauren S. Maeda, Ash A. Alizadeh, Ranjana H. Advani, Richard Hoppe, Steven R. Long, Brock Martin, Michael G. Ozawa, Michael S. Khodadoust, Hanlee P. Ji, Ronald Levy
Meeting Abstract
Hematology
Sarah Haebe, Tanaya Shree, Grady Day, Debra K. Czerwinski, Anuja Sathe, Susan M. Grimes, Steven R. Long, Brock Martin, Michael G. Ozawa, Hanlee P. Ji, Ronald Levy
Article
Oncology
Peter McLaughlin, Antonio J. Grillo-Lopez, Brain K. Link, Ronald Levy, Myron S. Czuczman, Michael E. Williams, Meyer R. Heyman, Isabelle Bence-Bruckler, Christine A. White, Fernando Cabanillas, Vinay Jain, Anthony D. Ho, John Lister, Key Wey, David Shen, Brain K. Dallaire
Summary: In this study, the chimeric anti-CD20 antibody IDEC-C2B8 was used to treat patients with relapsed low grade or follicular lymphoma. The response rate was 48%, comparable to single-agent cyto-toxic chemotherapy. Further research is needed to determine the efficacy of this agent and its potential use in combination with standard chemotherapy.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Biochemical Research Methods
Timothy R. Blake, Ole A. W. Haabeth, Adrienne Sallets, Rebecca L. McClellan, Trevor J. Del Castillo, Jose G. Vilches-Moure, Wilson C. Ho, Paul A. Wender, Ronald Levy, Robert M. Waymouth
Summary: Targeted delivery of nucleic acid therapeutics to the lungs shows promise for treating pulmonary diseases. New lysine-derived CART-mRNA complexes (K-CARTs/mRNA) demonstrate selective protein expression in the lungs without additives or targeting ligands. The ability to direct protein expression selectively in the spleen or lungs by simple changes to the CART structure opens new opportunities in research and gene therapy.
BIOCONJUGATE CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Niroz Abu-Saleh, Chiung-Chi Kuo, Wei Jiang, Ronald Levy, Shoshana Levy
Summary: Metastases are decreased in CD81KO mice. Moreover, a specific anti-CD81 antibody, 5A6, can inhibit metastasis in vivo and invasion and migration in vitro. Removing cholesterol or the intracellular domains of CD81 doesn't affect 5A6's inhibitory effect. The uniqueness of 5A6 is attributed to its recognition of a specific epitope on CD81's large extracellular loop. Finally, several CD81 membrane-associated partners, such as integrins and transferrin receptors, may contribute to the antimetastatic attributes of 5A6.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Susan M. Grimes, Heon Seok Kim, Sharmili Roy, Anuja Sathe, Carlos Ayala, Xiangqi Bai, Alison F. Almeda-Notestine, Sarah Haebe, Tanaya Shree, Ronald Levy, Billy T. Lau, Hanlee P. Ji
Summary: In this study, a single-cell method was developed to determine the genotypes of somatic alterations in coding regions of messenger RNAs and integrate these transcript-based variants with their corresponding cell transcriptomes. Nanopore adaptive sampling on single-cell complementary DNA libraries was used to validate coding variants in target gene transcripts, and short-read sequencing was used to characterize the cell types harboring the mutations. CRISPR edits for 16 targets were identified using a cancer cell line, and known variants in the cell line were validated using a 352-gene panel. Variants in primary cancer samples were validated using target gene panels ranging from 161 to 529 genes. A gene rearrangement was also identified in one patient, with the rearrangement occurring in two distinct tumor sites.
Meeting Abstract
Oncology
Caitlyn Miller, Idit Sagiv-Barfi, Patrick Neuhoefer, Debra Czerwinski, Carolyn Bertozzi, Jennifer Cochran, Ronald Levy
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Biochemistry & Molecular Biology
Caitlyn L. Miller, Idit Sagiv-Barfi, Patrick Neuhofer, Debra K. Czerwinski, Steven E. Artandi, Carolyn R. Bertozzi, Ronald Levy, Jennifer R. Cochran
Summary: Conjugating an immunostimulant with a tumor-targeted peptide improves the efficacy of systemically administered immunotherapy, transforming the immune-suppressive tumor microenvironment into a lymphocyte-rich environment. Furthermore, this treatment generates tumor-specific CD8(+)T cells.
CELL CHEMICAL BIOLOGY
(2022)
Article
Oncology
Tanaya Shree, Vishnu Shankar, Julian J. K. Lohmeyer, Debra K. Czerwinski, Joseph G. Schroers-Martin, Gladys M. Rodriguez, Sara Beygi, Alyssa M. Kanegai, Karen S. Corbelli, Etelka Gabriel, David M. Kurtz, Michael S. Khodadoust, Neel K. Gupta, Lauren S. Maeda, Ranjana H. Advani, Ash A. Alizadeh, Ronald Levy
Summary: In patients with lymphoma, the time since anti-CD20 treatment is an important predictor of neutralizing antibody response to COVID-19 vaccination. Comparing patients who received anti-CD20 treatment before or after vaccination, we demonstrate that vaccinating first can generate a durable antibody response that persists during anti-CD20-containing treatment.
BLOOD CANCER DISCOVERY
(2022)