Article
Immunology
Inigo Terren, Victor Sanda, Ainhoa Amarilla-Irusta, Ainara Lopez-Pardo, Arrate Sevilla, Gabirel Astarloa-Pando, Laura Amo, Olatz Zenarruzabeitia, Luca Scorrano, Francisco Borrego
Summary: Cytokine-induced memory-like (CIML) NK cells, stimulated with IL-12, IL-15 and IL-18, show promise in cancer immunotherapy. However, the mitochondrial dynamics of these cells remain unknown. This study found that IL-12/15/18 stimulation led to decreased viability and increased superoxide levels in NK cells, along with changes in mitochondrial morphology possibly mediated by decreased levels of OPA1 protein. While mitophagy was slightly impaired, an increase in autophagic flux was observed. These findings are important for improving the mitochondrial fitness and therapeutic efficacy of IL-12/15/18-stimulated NK cells.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Allergy
Linda Quatrini, Paola Vacca, Nicola Tumino, Francesca Besi, Anna Laura Di Pace, Francesca Scordamaglia, Stefania Martini, Enrico Munari, Maria Cristina Mingari, Sophie Ugolini, Lorenzo Moretta
Summary: The induction of PD-1 expression on human NK cells in the tumor setting is dependent on the cooperative action of glucocorticoids and cytokines, leading to enhanced mRNA translation and increased PD-1 levels.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Inigo Terren, Ane Orrantia, Alba Mosteiro, Joana Vitalle, Olatz Zenarruzabeitia, Francisco Borrego
Summary: NK cells acquire memory-like properties following stimulation with IL-12, IL-15 and IL-18, and these cytokine-induced memory-like NK cells have shown promising potential in cancer immunotherapy. NK cells modulate their metabolism in response to cytokine-stimulation, with a link between metabolism and cellular functions.
SCIENTIFIC REPORTS
(2021)
Article
Oncology
Celia C. Cubitt, Ethan McClain, Michelle Becker-Hapak, Jennifer A. Foltz, Pamela Wong, Julia A. Wagner, Carly C. Neal, Nancy D. Marin, Lynne Marsala, Mark Foster, Timothy Schappe, Patrick Soon-Shiong, John Lee, Melissa M. Berrien-Elliott, Todd A. Fehniger
Summary: This study describes the creation of a novel triple-cytokine fusion molecule, 18/12/TxM, using the N-803 scaffold fused to IL-18 and IL-12p70. The molecule exhibits trispecific cytokine activity and induces similar activation and memory-like differentiation of NK cells, as well as anti-tumor activity, compared to the individual cytokines.
MOLECULAR THERAPY-ONCOLYTICS
(2022)
Article
Oncology
Miriam Aarsund, Filip M. Segers, Yunjie Wu, Marit Inngjerdingen
Summary: This study compared the tumor-targeting potential of extracellular vesicles (EVs) derived from different sources of NK cells and found that EVs from activated primary NK cells or NK-92 cells have the best potential to infiltrate and target solid tumors.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2022)
Article
Medicine, Research & Experimental
Hung Le, Paul Spearman, Stephen N. Waggoner, Karnail Singh
Summary: Accumulation of activated NK cells in tissues during Ebola virus infection contributes to EVD pathogenesis. Immunization with Ebola VLPs provides rapid, NK cell-mediated protection against Ebola challenge. VP40 protein stimulates NK cell functions in an IL-12- and IL-18-dependent manner involving CD14(+) and CD14(-) accessory cells.
Article
Immunology
Kaveh Abdi, Karen Laky, Mehrnoosh Abshari, Elizabeth M. Hill, Larry Lantz, Nevil J. Singh, Eric O. Long
Summary: It has been found that NK cells produce IFN-gamma before the production of IL-12 by DCs in the early stage of immune response. Toll-like Receptor 4 (TLR4) on DCs and soluble factors produced by LPS-activated DCs play important roles in IFN-gamma production by NK cells.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2022)
Article
Immunology
Loredana Cifaldi, Ombretta Melaiu, Roberto Giovannoni, Monica Benvenuto, Chiara Focaccetti, Daniela Nardozi, Giovanni Barillari, Roberto Bei
Summary: DNAM-1 is a crucial NK cell activating receptor that contributes significantly to the killing of tumor or virus-infected cells by binding to specific ligands, alongside NKG2D and NCRs. DNAM-1 specifically recognizes PVR and Nectin-2 ligands expressed on a wide range of tumor cells and virus-infected cells. Although NK cells engineered with different antigen chimeric receptors or chimeric NKG2D receptors have been extensively studied, the use of DNAM-1 chimeric receptor-engineered NK cells has only been proposed in a recent proof-of-concept study. This perspective study aims to explain the rationale behind using this novel tool as a new anti-cancer immunotherapy.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Siyu Zhu, Chen Zhang, Qian Sun, Yang Wang, Wenwen Yu, Feng Wei, Xiubao Ren
Summary: This study establishes a CD3+CD56+ NKT-like cell model and investigates its role and mechanism in antitumor and antiviral immune responses through simulating the effects of cytokines.
JOURNAL OF ONCOLOGY
(2022)
Article
Oncology
Siyu Zhu, Chen Zhang, Qian Sun, Yang Wang, Wenwen Yu, Feng Wei, Xiubao Ren
Summary: Our study demonstrated that cytokines IL-12/15/18 can induce enhanced training immunity in CD3+CD56+ NKT-like cells, leading to a memory-like phenomenon characterized by increased IFN-gamma production, improved cell function, and proliferation potential. Additionally, IL-12/15/18 showed efficacy in promoting antitumor immune responses in NK-cell-sensitive tumor cells.
JOURNAL OF ONCOLOGY
(2022)
Article
Pharmacology & Pharmacy
Ruixin Sun, Yifan Liu, Chuanlong Wu, Min Zhou, Hong Luo, Guoxiu Du, Zhengyang Liu, Yansha Sun, Yiwei Dong, Jingwen Su, Mingliang Fan, Bizhi Shi, Hua Jiang, Zonghai Li
Summary: Previously, EGFRvIII-targeting CAR-T cells showed limited anti-tumor efficacy in treating advanced breast cancer, possibly due to reduced accumulation and persistence of therapeutic T cells. CXCR2 was found to significantly improve the trafficking and tumor specific accumulation of CAR-T cells, but weakened the anti-tumor effect due to T cell apoptosis. Co-expression of IL-15 or IL-18 in CXCR2 CAR-T cells effectively suppressed exhaustion and apoptosis, enhancing the anti-tumor activity without causing toxicity. These findings suggest a potential therapy strategy for advanced breast cancer in the future.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Caleb R. Glassman, Yamuna Kalyani Mathiharan, Kevin M. Jude, Leon Su, Ouliana Panova, Patrick J. Lupardus, Jamie B. Spangler, Lauren K. Ely, Christoph Thomas, Georgios Skiniotis, K. Christopher Garcia
Summary: The structural mechanism of receptor sharing used by IL-12 family cytokines can be utilized to tune the cytokine axis for therapeutics, as demonstrated by the design of IL-12 partial agonists that elicited anti-tumor immunity in vivo.
Article
Immunology
Valentina Mikhailova, Evgeniia Khokhlova, Polina Grebenkina, Zeina Salloum, Igor Nikolaenkov, Kseniya Markova, Alina Davidova, Sergey Selkov, Dmitriy Sokolov
Summary: NK cell development is influenced by their cellular microenvironment and cytokines, while their interaction with trophoblast cells can alter the NK cell phenotype and function. IL-15 and IL-18 play roles in modulating NK cell expression and cytotoxic activity, with IL-18 specifically enhancing NK-92 cell cytotoxicity against trophoblast cells.
Article
Multidisciplinary Sciences
Ting Lu, Rui Ma, Wenjuan Dong, Kun-Yu Teng, Daniel S. Kollath, Zhiyao Li, Jinhee Yi, Christian Bustillos, Shoubao Ma, Lei Tian, Anthony G. Mansour, Zhenlong Li, Erik W. Settles, Jianying Zhang, Paul S. Keim, Bridget M. Barker, Michael A. Caligiuri, Jianhua Yu
Summary: Engineered NK cells expressing soluble interleukin-15 and a chimeric antigen receptor targeting the spike protein of SARS-CoV-2 show promising potential as an off-the-shelf therapy for COVID-19 patients, with enhanced antiviral activity and cytotoxicity against spike protein-expressing cells.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Michelle K. Becker-Hapak, Niraj Shrestha, Ethan McClain, Michael J. Dee, Pallavi Chaturvedi, Gilles M. Leclerc, Lynne I. Marsala, Mark Foster, Timothy Schappe, Jennifer Tran, Sweta Desai, Carly C. Neal, Patrick Pence, Pamela Wong, Julia A. Wagner, David A. Russler-Germain, Xiaoyun Zhu, Catherine M. Spanoudis, Victor L. Gallo, Christian A. Echeverri, Laritza L. Ramirez, Lijing You, Jack O. Egan, Peter R. Rhode, Jin-an Jiao, Gabriela J. Muniz, Emily K. Jeng, Caitlin A. Prendes, Ryan P. Sullivan, Melissa M. Berrien-Elliott, Hing C. Wong, Todd A. Fehniger
Summary: NK cells show promise as a cellular therapy for cancer, but challenges in production of required reagents exist. A novel HFPC platform was developed to activate NK cells against cancer, showing potential for advancement in clinical GMP-grade memory-like NK cell production.
CANCER IMMUNOLOGY RESEARCH
(2021)
Review
Pharmacology & Pharmacy
Peter McMeekin, Dennis W. Lendrem, B. Clare Lendrem, Arthur G. Pratt, Richard Peck, John D. Isaacs, David Jones
DRUG DISCOVERY TODAY
(2020)
Letter
Medicine, General & Internal
Ewan Hunter, David A. Price, Elizabeth Murphy, Ina Schim van der Loeff, Kenneth F. Baker, Dennis Lendrem, Clare Lendrem, Matthias L. Schmid, Lucia Pareja-Cebrian, Andrew Welch, Brendan A. I. Payne, Christopher J. A. Duncan
Article
Chemistry, Analytical
Sara Graziadio, Amanda Winter, B. Clare Lendrem, Jana Suklan, William S. Jones, Samuel G. Urwin, Rachel A. O'Leary, Rachel Dickinson, Anna Halstead, Kasia Kurowska, Kile Green, Andrew Sims, A. John Simpson, H. Michael Power, A. Joy Allen
Review
Immunology
Aline Pfefferle, Benedikt Jacobs, Alvaro Haroun-Izquierdo, Lise Kveberg, Ebba Sohlberg, Karl-Johan Malmberg
FRONTIERS IN IMMUNOLOGY
(2020)
Review
Immunology
Marius Farcas, Marit Inngjerdingen
SCANDINAVIAN JOURNAL OF IMMUNOLOGY
(2020)
Article
Immunology
Rachel E. Crossland, Jean Norden, Sakhila Ghimire, Mateja Kralj Juric, Kim F. Pearce, Clare Lendrem, Matthew Collin, Eva Mischak-Weissinger, Ernst Holler, Hildegard T. Greinix, Anne M. Dickinson
Summary: The study found that miR-155 and miR-146a were upregulated in gastrointestinal and skin tissue samples of aGvHD patients, and their expression levels in serum and urine samples were also associated with the risk of developing aGvHD. These results support the potential of miR-155 and miR-146a as biomarkers for aGvHD, but further investigation is needed to understand their role in generalized inflammation and specific pathophysiology.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Respiratory System
Basem Al-Omari, Peter McMeekin, A. Joy Allen, Ahsan R. Akram, Sara Graziadio, Jana Suklan, William S. Jones, B. Clare Lendrem, Amanda Winter, Milo Cullinan, Joanne Gray, Kevin Dhaliwal, Timothy S. Walsh, Thomas H. Craven
Summary: In VAP research, reference standards typically require microbiological confirmation, with BAL culture being the most commonly used reference standard.
BMC PULMONARY MEDICINE
(2021)
Article
Oncology
Miriam Aarsund, Filip M. Segers, Yunjie Wu, Marit Inngjerdingen
Summary: This study compared the tumor-targeting potential of extracellular vesicles (EVs) derived from different sources of NK cells and found that EVs from activated primary NK cells or NK-92 cells have the best potential to infiltrate and target solid tumors.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2022)
Article
Medicine, General & Internal
Jessica Tarn, Dennis Lendrem, Peter McMeekin, Clare Lendrem, Ben Hargreaves, Wan-Fai Ng
Summary: In patients with pSS, symptom burden and NSST subgroup, rather than systemic disease activity, are significantly associated with HRQoL longitudinally. Improvements in symptom burden have the potential to produce significant impacts on long-term HRQoL in pSS.
JOURNAL OF INTERNAL MEDICINE
(2022)
Article
Multidisciplinary Sciences
Wei-Yu Lin, Sarah E. Fordham, Eric Hungate, Nicola J. Sunter, Claire Elstob, Yaobo Xu, Catherine Park, Anne Quante, Konstantin Strauch, Christian Gieger, Andrew Skol, Thahira Rahman, Lara Sucheston-Campbell, Junke Wang, Theresa Hahn, Alyssa I. Clay-Gilmour, Gail L. Jones, Helen J. Marr, Graham H. Jackson, Tobias Menne, Mathew Collin, Adam Ivey, Robert K. Hills, Alan K. Burnett, Nigel H. Russell, Jude Fitzgibbon, Richard A. Larson, Michelle M. Le Beau, Wendy Stock, Olaf Heidenreich, Abrar Alharbi, David J. Allsup, Richard S. Houlston, Jean Norden, Anne M. Dickinson, Elisabeth Douglas, Clare Lendrem, Ann K. Daly, Louise Palm, Kim Piechocki, Sally Jeffries, Martin Bornhauser, Christoph Rollig, Heidi Altmann, Leo Ruhnke, Desiree Kunadt, Lisa Wagenfuhr, Heather J. Cordell, Rebecca Darlay, Mette K. Andersen, Maria C. Fontana, Giovanni Martinelli, Giovani Marconi, Miguel A. Sanz, Jose Cervera, Ines Gomez-Segui, Thomas Cluzeau, Chimene Moreilhon, Sophie Raynaud, Heinz Sill, Maria Teresa Voso, Francesco Lo-Coco, Herve Dombret, Meyling Cheok, Claude Preudhomme, Rosemary E. Gale, David Linch, Julia Gaal-Wesinger, Andras Masszi, Daniel Nowak, Wolf-Karsten Hofmann, Amanda Gilkes, Kimmo Porkka, Jelena D. Milosevic Feenstra, Robert Kralovics, David Grimwade, Manja Meggendorfer, Torsten Haferlach, Szilvia Krizsan, Csaba Bodor, Friedrich Stolzel, Kenan Onel, James M. Allan
Summary: The study conducted a genome-wide association analysis on European patients with AML, identifying genetic loci associated with the risk of developing the disease. The results shed light on potential functional genes involved in histone methylation and immune function in AML etiology.
NATURE COMMUNICATIONS
(2021)
Correction
Multidisciplinary Sciences
Wei-Yu Lin, Sarah E. Fordham, Eric Hungate, Nicola J. Sunter, Claire Elstob, Yaobo Xu, Catherine Park, Anne Quante, Konstantin Strauch, Christian Gieger, Andrew Skol, Thahira Rahman, Lara Sucheston-Campbell, Junke Wang, Theresa Hahn, Alyssa I. Clay-Gilmour, Gail L. Jones, Helen J. Marr, Graham H. Jackson, Tobias Menne, Mathew Collin, Adam Ivey, Robert K. Hills, Alan K. Burnett, Nigel H. Russell, Jude Fitzgibbon, Richard A. Larson, Michelle M. Le Beau, Wendy Stock, Olaf Heidenreich, Abrar Alharbi, David J. Allsup, Richard S. Houlston, Jean Norden, Anne M. Dickinson, Elisabeth Douglas, Clare Lendrem, Ann K. Daly, Louise Palm, Kim Piechocki, Sally Jeffries, Martin Bornhauser, Christoph Rollig, Heidi Altmann, Leo Ruhnke, Desiree Kunadt, Lisa Wagenfuhr, Heather J. Cordell, Rebecca Darlay, Mette K. Andersen, Maria C. Fontana, Giovanni Martinelli, Giovanni Marconi, Miguel A. Sanz, Jose Cervera, Ines Gomez-Segui, Thomas Cluzeau, Chimene Moreilhon, Sophie Raynaud, Heinz Sill, Maria Teresa Voso, Francesco Lo-Coco, Herve Dombret, Meyling Cheok, Claude Preudhomme, Rosemary E. Gale, David Linch, Julia Gaal-Wesinger, Andras Masszi, Daniel Nowak, Wolf-Karsten Hofmann, Amanda Gilkes, Kimmo Porkka, Jelena D. Milosevic Feenstra, Robert Kralovics, David Grimwade, Manja Meggendorfer, Torsten Haferlach, Szilvia Krizsan, Csaba Bodor, Friedrich Stolzel, Kenan Onel, James M. Allan
NATURE COMMUNICATIONS
(2022)
Article
Immunology
Margherita Boieri, Anna Malishkevich, Ranya Guennoun, Emanuela Marchese, Sanne Kroon, Kathryn E. E. Trerice, Mary Awad, Jong Ho Park, Sowmya Iyer, Johannes Kreuzer, Wilhelm Haas, Miguel N. N. Rivera, Shadmehr Demehri
Summary: This study demonstrates the important role of CD4(+) Th2 cells in immunity against breast cancer by forcing the cancer cells to terminally differentiate. Th2 cells directly block breast carcinogenesis by secreting specific cytokine signals, transforming high-grade breast tumors into low-grade, fibrocystic-like structures.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Article
Mathematical & Computational Biology
Kevin J. Wilson, S. Faye Williamson, A. Joy Allen, Cameron J. Williams, Thomas P. Hellyer, B. Clare Lendrem
Summary: This article proposes a novel Bayesian approach to determine the sample size for the diagnostic accuracy study, utilizing information from the analytical validity stage. The approach uses assurance to calculate the required sample size based on the target width of a posterior probability interval and allows for the choice of using or disregarding the data from the analytical validity study. Sensitivity analyses and evaluations of prior-data conflict are performed to assess the robustness of the proposed method. The results demonstrate that the assurance-based approach can reduce the required sample size when suitable prior information is available.
STATISTICS IN MEDICINE
(2022)
Letter
Biophysics
Callum Wright, Ginette Reid, Beverley Clare Lendrem, Erin Hurst, Amy Publicover, Rachel Luke, Louise Duncan, Venetia Bigley, Matthew Collin
BONE MARROW TRANSPLANTATION
(2023)
Article
Respiratory System
A. Joy Allen, Andrea Gonzalez-Ciscar, Clare Lendrem, Jana Suklan, Karen Allen, Ashley Bell, Frances Baxter, Stephen Crulley, Louise Fairlie, Danielle Hardy, Louise Johnston, Joanne McKenna, Nicole Richards, Gavin Shovlin, Clare Simmister, Sheila Waugh, Philip Woodsford, Sara Graziadio, Michael Power, A. John Simpson, Prashant Kumar, Katherine Eastham, Malcolm Brodlie