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
Manojkumar Gunasekaran, Andrea Difiglia, John Fitzgerald, Robert Hariri, William van der Touw, Tanel Mahlakoiv
Summary: Researchers have found that NK cells derived from human placental hematopoietic stem cells (CYNK) have strong antiviral effects against Influenza A virus (IAV) infection and can enhance the expression of NK cell activating ligands on respiratory epithelial cells. Co-culture of CYNK cells with IAV-infected cells showed increased degranulation and cytotoxicity against the virus.
FRONTIERS IN IMMUNOLOGY
(2022)
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
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
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
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
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
Immunology
Yuhan Sun, Alexander James Sedgwick, Md Abdullah-Al-Kamran Khan, Yaseelan Palarasah, Stefano Mangiola, Alexander David Barrow
Summary: The activation of NK cell function in bladder cancer is regulated by cytokines and secreted factors. IL-2-expanded NK cell phenotype is associated with improved prognosis, while PDGF-DD-activated NK cell phenotype is associated with poor prognosis. High expression of activating NK cell receptors correlates with IL-2-expanded NK cell phenotype and improved prognosis in bladder cancer.
FRONTIERS IN IMMUNOLOGY
(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
Cell Biology
Joonbeom Bae, Longchao Liu, Casey Moore, Eric Hsu, Anli Zhang, Zhenhua Ren, Zhichen Sun, Xue Wang, Jiankun Zhu, Jiao Shen, Jian Qiao, Yang-Xin Fu
Summary: This study highlights the essential role of endogenous IL-2 in immune checkpoint blockade-based immunotherapy and reveals the correlation between insufficient IL-2 signaling and T-cell exhaustion during tumor progression. The study also demonstrates that engineered mesenchymal stem cells (MSCs) delivering IL-2 can overcome ICB resistance and elicit anti-tumor immunity without toxicity. Engineered MSCs rejuvenate CD8(+) tumor-infiltrating lymphocytes (TILs) and potentiate the effects of ICB and chemotherapy.
NATURE CELL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Zhe Huang, Seung Goo Kang, Yunqiao Li, Jaroslav Zak, Namir Shaabani, Kaiyuan Deng, Jovan Shepherd, Raag Bhargava, John R. Teijaro, Changchun Xiao
Summary: Inhibition of IFN-I signaling in NK cells enhances the responses of CD4 and CD8 T cells, promotes humoral immune responses, and thereby facilitates the control of persistent virus infection.
Article
Medicine, Research & Experimental
Yong-Hyun Joo, Yeong-Geun Lee, Younghyun Lim, Hoyeon Jeon, In-Gu Lee, Yong -Bin Cho, So-Hee Hong, Eui Ho Kim, Soon Ho Choi, Jung-Woong Kim, Se Chan Kang, Young-Jin Seo
Summary: This study investigated the anti-influenza A virus (IAV) activity of an aqueous mixture of Agrimonia pilosa and Galla rhois extracts (APRG64). The results showed that APRG64 significantly reduced IAV-induced cytopathic effect, viral protein transcription/expression, and infectious viral particle production. The main component responsible for the anti-IAV activity was identified as apigenin. APRG64 and apigenin inhibited virus attachment, entry, and polymerase activity. Intranasal or oral administration of APRG64 reduced viral loads and protected mice from IAV-induced mortality by reducing viral RNA levels and pro-inflammatory cytokine expression in the lungs.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Review
Parasitology
Sepideh Mahmoudzadeh, Hojjatollah Nozad Charoudeh, Claudia Silva Marques, Saeed Bahadory, Ehsan Ahmadpour
Summary: Natural Killer cells play a crucial protective role during Toxoplasma gondii infection by releasing interferon gamma. Interleukin 12 is a critical cytokine for generating IFN-gamma-producing NK cells, and IL-2 is an important stimulatory factor for NK cells. Factors affecting the stimulation of interleukin-12 production by T. gondii tachyzoites were also discussed in the review.
PARASITOLOGY RESEARCH
(2021)
Article
Immunology
Avishai Shemesh, Harry Pickering, Kole T. Roybal, Lewis L. Lanier
Summary: Low IL-12 concentrations are sufficient for the expansion of human NK cells through innate-activating NK receptor-orchestrated differential IL-12 signalling. This study demonstrates that activating NK receptor stimulation promotes differential IL-12 signalling, leading to human NK cell expansion.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Article
Medicine, Research & Experimental
Won-Kyung Cho, Jin Yeul Ma
Summary: Epimedium koreanum Nakai (EKN) has shown significant inhibitory effects on influenza A virus infection by directly blocking viral attachment and having a virucidal effect. It can potentially be developed as a natural viral inhibitor against influenza virus infection.
BIOMEDICINE & PHARMACOTHERAPY
(2022)