Article
Immunology
Haoxian Gou, Shenglu Liu, Linxin Liu, Ming Luo, Shu Qin, Kai He, Xiaoli Yang
Summary: Hepatocellular carcinoma (HCC) is a common and deadly liver malignancy. This study confirms that liver sinusoidal endothelial cells (LSEC) secrete CXCL16, which promotes the accumulation of CXCR6(+) NKT cells in the liver and has potent antitumor effects. High expression of CXCL16 is associated with activated NKT cells and increased interferon-gamma (IFN-gamma) production. The combination of a farnesoid X receptor agonist and a takeda G protein coupled receptor 5 antagonist exhibits significant tumor suppressive effects in an orthotopic liver tumor model, possibly through the CXCL16/CXCR6 axis.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Takahiro Miyazaki, Mekhala Maiti, Marlene Hennessy, Thomas Chang, Peiwen Kuo, Murali Addepalli, Palakshi Obalapur, Sara Sheibani, Joanna Wilczek, Rhoneil Pena, Phi Quach, Janet Cetz, Andrew Moffett, Yinyan Tang, Peter Kirk, Jicai Huang, Dawei Sheng, Ping Zhang, Werner Rubas, Loui Madakamutil, Saul Kivimae, Jonathan Zalevsky
Summary: NKTR-255, a novel polyethylene glycol-conjugate of rhIL-15, displayed similar in vitro properties to rhIL-15 but differed from precomplexed cytokines. NKTR-255 showed enhanced PK properties with prolonged IL-15R engagement, resulting in sustained proliferation and activation of NK and CD8(+) T cells. Furthermore, NKTR-255 demonstrated superior antitumor activity in a B-cell lymphoma model compared to precomplexed cytokines.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Immunology
Guangwei Cui, Akihiro Shimba, Jianshi Jin, Taisaku Ogawa, Yukiko Muramoto, Hitoshi Miyachi, Shinya Abe, Takuma Asahi, Shizue Tani-Ichi, Johannes M. Dijkstra, Yayoi Iwamoto, Kirill Kryukov, Yuanbo Zhu, Daichi Takami, Takahiro Hara, Satsuki Kitano, Yan Xu, Hajime Morita, Moyu Zhang, Lynn Zreka, Keishi Miyata, Takashi Kanaya, Shinya Okumura, Takashi Ito, Etsuro Hatano, Yoshimasa Takahashi, Hiroshi Watarai, Yuichi Oike, Tadashi Imanishi, Hiroshi Ohno, Toshiaki Ohteki, Nagahiro Minato, Masato Kubo, Georg A. Hollander, Hideki Ueno, Takeshi Noda, Katsuyuki Shiroguchi, Koichi Ikuta
Summary: This study reveals a circulating subset of iNKT cells, C2 iNKT cells, with NK cell-like properties distinct from conventional tissue-resident iNKT cells. C2 iNKT cells protect against tumor metastasis and promote antiviral immune responses.
SCIENCE IMMUNOLOGY
(2022)
Article
Immunology
Mitch Ganley, Lauren E. Holz, Jordan J. Minnell, Maria N. de Menezes, Olivia K. Burn, Kean Chan Yew Poa, Sarah L. Draper, Kieran English, Susanna T. S. Chan, Regan J. Anderson, Benjamin J. Compton, Andrew J. Marshall, Anton Cozijnsen, Yu Cheng Chua, Zhengyu Ge, Kathryn J. Farrand, John C. Mamum, Calvin Xu, Ian A. Cockburn, Katsuyuki Yui, Patrick Bertolino, Stephanie Gras, Jerome Le Nours, Jamie Rossjohn, Daniel Fernandez-Ruiz, Geoffrey I. McFadden, David F. Ackerley, Gavin F. Painter, Ian F. Hermans, William R. Heath
Summary: Malaria, caused by Plasmodium species transmitted by mosquitoes, can be prevented by inducing liver-resident memory T cells through mRNA vaccines. Addition of an agonist that recruits T cell help improved the efficacy of the vaccine. This strategy shows potential in malaria-endemic regions.
Article
Immunology
Helen R. Wagstaffe, Omu Anzala, Hannah Kibuuka, Zacchaeus Anywaine, Sodiomon B. Sirima, Rodolphe Thiebaut, Laura Richert, Yves Levy, Christine Lacabaratz, Viki Bockstal, Kerstin Luhn, Macaya Douoguih, Martin R. Goodier
Summary: This study assesses the NK cell phenotype and function in African trial participants with universal exposure to HCMV, and reveals consistent changes in NK cell phenotypic composition and robust antibody-dependent NK cell function after heterologous two-dose Ebola vaccination.
Article
Immunology
Keun Young Min, Jimo Koo, Geunwoong Noh, Dajeong Lee, Min Geun Jo, Ji Eon Lee, Minseong Kang, Seung Yeun Hyun, Wahn Soo Choi, Hyuk Soon Kim
Summary: This study investigated the role of the TGF-beta-producing CD1d(hi)PD-L1(hi)CD27(+) NK subset in suppressing T(H)2 immunity and ILC2 activation in AD mice, and found a close association between the function of this NK subset and the severity of AD.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Cell Biology
Xiang Li, Chen Jin, Qi Chen, Xihua Zheng, Di Xie, Qielan Wu, Lu Wang, Shiyu Bai, Huimin Zhang, Li Bai
Summary: Invariant NK T (iNKT) cells are enriched in the liver, where a liver-specific CD24(+) iNKT subset with high proliferation and metabolism activity is found but lower granzyme B production. The liver microenvironment also influences the differentiation of conventional T cells, leading to the generation of CD24(+) T cells with different functional characteristics. These findings suggest that the liver microenvironment may induce the generation of a liver-specific iNKT subset that plays a crucial role in maintaining liver homeostasis.
JOURNAL OF LEUKOCYTE BIOLOGY
(2022)
Review
Oncology
Fengyun Zhong, Yilin Lin, Xiangxiang Jing, Yingjiang Ye, Shan Wang, Zhanlong Shen
Summary: The immune microenvironment and immunotherapies of colorectal cancer (CRC) have attracted extensive attention, with a focus on T cells. However, innate immune cells such as NK cells, NKT cells, and gamma 8T cells also play important roles in CRC. The anti-tumorigenic and pro-tumorigenic mechanisms of these cells are still under investigation, and immunotherapies utilizing these cells have shown efficacy in animal models and are being explored in clinical trials.
Article
Immunology
Nicolas Krause, Joerg Mengwasser, Elpida Phithak, Francisca Beato, Marc Appis, Edgar Louis Milford, Johan Pratschke, Igor Sauer, Anja Kuehl, Arndt Vogel, Michael Goodyear, Linda Hammerich, Frank Tacke, Johanna Faith Haas, Tobias Mueller, Nalan Utku
Summary: IR1 cells are a subset of T regulatory cells that have immune suppressive functions and can inhibit proliferation in mixed lymphocyte reactions. They deliver regulatory signals by binding to their ligand, HLA-DR alpha 2, and have the potential to modulate immune dysregulation.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Kevin Aviles-Padilla, Laura S. Angelo, Dwight Fan, Silke Paust
Summary: NKG2C(+) and CXCR6(+) NK cell subsets in pediatric transplant recipients have distinct phenotypes and effector functions. The majority of post-transplant NK cells are NKG2C-CXCR6-, despite the ability of NKG2C(+) NK cells to provide immune memory. CXCR6(+) NK cells, although phenotypically less differentiated, are highly proliferative and capable of producing IFN-gamma and TNF alpha.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Cell Biology
Sophia Papaioannou, Jia-Xiang See, Mingeum Jeong, Carolina De La Torre, Volker Ast, Philipp-Sebastian Reiners-Koch, Ankita Sati, Carolin Mogler, Michael Platten, Adelheid Cerwenka, Ana Stojanovic
Summary: Liver sinusoidal endothelial cells (LSECs) respond to LPS and immune-derived signals, producing chemokines CCL2 and CXCL10. NK cells exposed to LSECs in vitro are primed for higher production of IFN-g in response to IL-12 and IL-18. In inflamed livers, NK cells are the major producers of IFN-g. This positive feedback loop of immune cell attraction and activation is regulated by LSECs and is important in liver inflammation.
Review
Oncology
Xiao-Peng Tian, Yi Cao, Jun Cai, Yu-Chen Zhang, Qi-Hua Zou, Jin-Ni Wang, Yu Fang, Jia-Hui Wang, Song-Bin Guo, Qing-Qing Cai
Summary: The increasing use of high-throughput screening has greatly advanced our knowledge on the molecular basis of natural killer/T-cell lymphoma (NKTCL) and revolutionized its treatment. Asparaginase-containing regimens have significantly improved survival outcomes in NKTCL patients. Novel treatment strategies, including targeted antibodies, immune checkpoint inhibitors, and chimeric antigen receptor T cells, are currently being developed for NKTCL and show promising potential for future use.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2023)
Article
Pharmacology & Pharmacy
Amal Elhage, Peter Cuthbertson, Chloe Sligar, Debbie Watson, Ronald Sluyter
Summary: Graft-versus-host disease (GVHD) is a fatal inflammatory disorder resulting from allogeneic hematopoietic stem cell transplantation. This study demonstrates that blocking the P2X7 receptor with a specific monoclonal antibody reduces the development of GVHD in humanized mice.
Article
Medicine, Research & Experimental
Priyanka Rawat, Asmita Das
Summary: NK cells play important immune functions in autoimmune diseases and successful pregnancies, providing immunity against viral infections and tumors. They are distributed in various organs and exhibit functional differences due to the regulation of transcription factors.
Article
Oncology
Irene Veneziani, Claudia Alicata, Andrea Pelosi, Nadine Landolina, Biancamaria Ricci, Valentina D'Oria, Anna Fagotti, Giovanni Scambia, Lorenzo Moretta, Enrico Maggi
Summary: The study suggests that TLR8 in NK cells may serve as a potential target for immunotherapy in patients with cancer.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Review
Oncology
Josep M. Llovet, Florian Castet, Mathias Heikenwalder, Mala K. Maini, Vincenzo Mazzaferro, David J. Pinato, Eli Pikarsky, Andrew X. Zhu, Richard S. Finn
Summary: Liver cancer, specifically hepatocellular carcinoma (HCC), is the second leading cause of cancer-related death globally. Traditional treatments involve specific drugs, but the emergence of immune checkpoint inhibitors has revolutionized the management of HCC.
NATURE REVIEWS CLINICAL ONCOLOGY
(2022)
Editorial Material
Medicine, General & Internal
Victoria Male
BMJ-BRITISH MEDICAL JOURNAL
(2022)
Review
Obstetrics & Gynecology
Ee Von Woon, Orene Greer, Nishel Shah, Dimitrios Nikolaou, Mark Johnson, Victoria Male
Summary: Studies have found significantly increased levels of uterine natural killer cells in women with recurrent miscarriage and recurrent implantation failure, which may contribute to implantation or placental development failure. While results on cytokine secretion varied among studies, most research indicated lower expression of inhibitory receptors and higher expression of angiogenic factors in women with recurrent miscarriage.
HUMAN REPRODUCTION UPDATE
(2022)
Review
Immunology
Laura J. Pallett, Mala K. Maini
Summary: This article reviews the characteristics and functions of liver-specific memory T cells, including their residency and adaptation to the hepatic microenvironment, as well as their interactions with other cell types. Additionally, the importance of liver sampling for disease monitoring and targeted immunotherapy is discussed.
SEMINARS IN IMMUNOPATHOLOGY
(2022)
Article
Immunology
Emily M. Whettlock, Ee Woon, Antonia O. Cuff, Brendan Browne, Mark R. Johnson, Victoria Male
Summary: Uterine natural killer cells (uNK) have been found to play an important role in regulating pregnancy. Recent studies have shown that uNK can be divided into three subsets, each with different functions during pregnancy. These subsets are most active during the secretory phase of the menstrual cycle and have the highest frequency of interaction with placental cells. This research provides important insights for studying subfertility, recurrent miscarriage, pre-eclampsia, and pre-term labor.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Mariana O. Diniz, Elena Mitsi, Leo Swadling, Jamie Rylance, Marina Johnson, David Goldblatt, Daniela Ferreira, Mala K. Maini
Summary: T cells can contribute to clearance of respiratory viruses and provide long-lasting protection. Pre-existing cross-reactive T cell responses play a crucial role in resisting infection. Airway-resident T cells with cross-reactivity to SARS-CoV-2 have been found in healthy individuals, suggesting their potential use in mucosal vaccines.
Review
Immunology
Victoria Male, Ashley Moffett
Summary: The presence of granulated lymphocytes known as uNK cells in the human uterine mucosa was first noted in the nineteenth century, but they were identified as a type of NK cell in 1990. Uterine NK cells have been found to be less cytotoxic than their peripheral counterparts. Recent research has identified three subpopulations of uNK cells that cluster separately from peripheral NK cells. This review examines the history of uNK cell research, their interactions with placental cells, their role in placental implantation, and their potential for defending against infection and mediating memory effects.
ANNUAL REVIEW OF IMMUNOLOGY
(2023)
Review
Gastroenterology & Hepatology
Seng Gee Lim, Thomas F. Baumert, Carolina Boni, Ed Gane, Massimo Levrero, Anna S. Lok, Mala K. Maini, Norah A. Terrault, Fabien Zoulim
Summary: Functional cure of chronic hepatitis B (CHB), achieved through hepatitis B surface antigen (HBsAg) loss after 24 weeks off therapy, is the goal of current treatment. However, the rarity of achieving this cure with current therapy highlights the need for novel approaches. The three categories of treatment include reducing viral replication, reducing antigen load, and immunotherapies. Combination therapy of nucleos(t)ide analogues and immunotherapy shows promise in reducing HBsAg levels and inducing HBsAg loss in some patients, particularly those with low baseline HBsAg levels. Monitoring during therapy using viral and immunological biomarkers is important to predict HBsAg loss and understand its mechanisms.
NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY
(2023)
Editorial Material
Multidisciplinary Sciences
Victoria Male
Editorial Material
Cell Biology
Victoria Male
IMMUNOLOGY AND CELL BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Daniel M. Altmann, Catherine J. Reynolds, George Joy, Ashley D. Otter, Joseph M. Gibbons, Corinna Pade, Leo Swadling, Mala K. Maini, Tim Brooks, Amanda Semper, Aine Mcknight, Mahdad Noursadeghi, Charlotte Manisty, Thomas A. Treibel, James C. Moon, Rosemary J. Boyton
Summary: This study analyzes the immune response in healthcare workers with mild or asymptomatic SARS-CoV-2 infection and compares it to those with Long Covid. The results show no significant differences in immune responses between the two groups up to 18 weeks post-infection and 1 year after vaccination, suggesting that immune response variations are unlikely to be a contributing factor to Long Covid development.
NATURE COMMUNICATIONS
(2023)
Article
Immunology
Ee Von Woon, Dimitrios Nikolaou, Kate MacLaran, Julian Norman-Taylor, Priya Bhagwat, Antonia O. O. Cuff, Mark R. R. Johnson, Victoria Male
Summary: A significant proportion of unexplained reproductive failure is associated with immunological dysfunction at the maternal-fetal interface. Uterine Natural Killer cells (uNK) play a crucial role in successful pregnancy by regulating EVT invasion and spiral artery remodeling. This study explores the frequency, phenotype, and function of uNK subsets in women with unexplained reproductive failure and reveals a global reduction in expression of uNK receptors important for interaction with HLA-C and HLA-G, leading to reduced uNK activation.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Rheumatology
Mala K. Maini
Summary: This conference report highlights the potential of targeting tissue-resident T cells to enhance vaccine immunity. The researchers found that liver-resident NK cells can constrain therapeutic vaccine-induced HBV-specific T cells, but cytokine-activation and PD-L1 blockade can convert them into helpers that boost the HBV-specific T cells. It was also discovered that tissue-resident T cells in the lung can include cells that recognize SARS-CoV-2, including cross-reactive responses present before the pandemic. The selective expansion of T cells without detectable antibodies in some donors who aborted SARS-CoV-2 infection underscores the importance of inducing T cells with future prophylactic vaccines.
SEMINARS IN ARTHRITIS AND RHEUMATISM
(2023)
Article
Public, Environmental & Occupational Health
Alexandra Alvergne, Ee Von Woon, Victoria Male
Summary: COVID-19 vaccination may lengthen the menstrual cycle, potentially mediated by disturbances in ovarian hormones. However, no clear association was found between the timing of vaccination within the menstrual cycle and menstrual changes.
FRONTIERS IN REPRODUCTIVE HEALTH
(2022)
Article
Immunology
Victoria Male
Summary: This article discusses the risks of SARS-CoV-2 infection during pregnancy and the role of vaccination in reducing these risks. Many pregnant individuals have concerns about the safety of vaccines, but existing data confirm the safety and efficacy of COVID-19 vaccines during pregnancy.
NATURE REVIEWS IMMUNOLOGY
(2022)
