Review
Immunology
Hyoungjun Ham, Michael Medlyn, Daniel D. Billadeau
Summary: NK cell-mediated cytotoxicity is essential for protection from infections and cancer, involving lytic granule development and degranulation processes. Studies on molecular regulations of NK cell cytotoxicity are providing insights into improving anti-cancer therapies and discovering new therapeutic opportunities.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Erica A. Steen, Kim E. Nichols, Lauren K. Meyer
Summary: Familial hemophagocytic lymphohistiocytosis (fHLH) is a group of rare inherited immune dysregulation disorders characterized by mutations in genes involved in cytotoxic granules in CD8+ T cells and NK cells. This defect leads to sustained lymphocyte activation and excessive secretion of pro-inflammatory cytokines, resulting in tissue damage and multi-organ failure. Studies in murine models have provided insights into the mechanisms underlying hyperinflammation in fHLH.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Joseph Andrew Clara, Emily R. Levy, Robert Reger, Stefan Barisic, Long Chen, Elena Cherkasova, Mala Chakraborty, David S. J. Allan, Richard Childs
Summary: This study developed an efficient gene editing platform using CRISPR/Cas9 technology to disrupt the CD38 gene and insert the CD16 receptor, enhancing the antibody-dependent cellular cytotoxicity (ADCC) and resistance to daratumumab of NK cells. The results showed that CD38(KO)/CD16(KI) NK cells exhibited enhanced anti-myeloma activity in vitro and in vivo. This study provides a strong rationale for exploring the clinical application of adoptive immunotherapy using gene-edited NK cells.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Oncology
Rui Zhang, Qingxi Liu, Sa Zhou, Hongpeng He, Mingfeng Zhao, Wenjian Ma
Summary: In this study, a genetically modified bifunctional CAR-NK cell therapy was developed for the treatment of acute myeloid leukemia (AML). The bifunctional CD33/B16 CAR-NK cells showed superior killing efficiency towards AML cells compared to CAR-NK cells targeting CD33 only. In vivo studies also demonstrated effective clearance of leukemic cells and improved survival. These findings suggest a promising CAR-NK approach for AML treatment and potentially other tumors.
Article
Medicine, General & Internal
Laura Strobel, Kilian Vomstein, Christiana Kyvelidou, Susanne Hofer-Tollinger, Katharina Feil, Ruben-Jeremias Kuon, Susanne Ebner, Jakob Troppmair, Bettina Toth
Summary: In this study, we found that compared to sRPL patients, sCtrls had higher numbers of CD56(+) and CD56(dim)CD16(bright) cells. Furthermore, sRPL patients had lower numbers of CD56(dim)CD16(bright)NKG2D(+) and CD56(dim)CD16(bright)NKp46(+) compared to sCtrls.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Biochemical Research Methods
Sagar N. Agnihotri, Giovanni Stefano Ugolini, Matthew Ryan Sullivan, Yichao Yang, Agustin De Ganzo, Ji Won Lim, Tania Konry
Summary: Most common cellular analysis methods employ a top-down approach, which destroys the cell and prevents correlation between genomics and functional assays. This study presents a bottom-up approach using single-cell tools, allowing functional phenotyping through observing cytotoxicity and probing underlying biology.
Article
Environmental Sciences
Yufan Zhang, Yifan Zhao, Yue Zhai, Jinyi He, Mengke Tang, Yalin Liu, Ye Yao, Peng Xue, Miao He, Qian Li, Yanyi Xu, Weidong Qu, Yubin Zhang
Summary: This study aimed to investigate the impact of cadmium (Cd) on natural killer (NK) cells. It was found that Cd treatment impaired the differentiation of NK progenitors in the bone marrow but activated the JAK3/STAT5 signaling to drive the proliferation of mature NK (mNK) cells. Cd treatment bidirectionally regulated the cytotoxicity of mNK cells to tumor cells through the modulation of Fas expression and granzyme B expression. Similar effects were observed in human mNK cells. This research extends our understanding of the immunotoxicity of Cd.
Article
Allergy
Lori Broderick, Gwendolyn M. Clay, Robert H. Blum, Yang Liu, Rachael McVicar, Fabio Papes, Laela M. Booshehri, Ian G. Cowell, Caroline A. Austin, Christopher D. Putnam, Dan S. Kaufman
Summary: The study examines the impact of Hoffman syndrome-associated mutations in TOP2B on the development and function of NK cells. Using a knockin murine model and patient-derived iPSCs, the researchers investigated NK-cell development in mouse bone marrow and spleen, and assessed the immunophenotype, gene expression, and cytotoxic activity of NK cells in both murine and human models.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2022)
Article
Immunology
Lukman O. Afolabi, Jiacheng Bi, Liang Chen, Xiaochun Wan
Summary: The study demonstrated that Piperlongumine (PL), a natural alkaloid obtained from long pepper fruit, has both antitumor and immunomodulatory potential on all tested tumors, increasing tumor susceptibility to NK cell cytolysis. This suggests that PL could be explored as a complementary approach to NK cell immunotherapy for cancer treatment.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Latiffa Amniai, Coline Ple, Mathieu Barrier, Patricia de Nadai, Philippe Marquillies, Han Vorng, Cecile Chenivesse, Anne Tsicopoulos, Catherine Duez
Summary: The study found that CCL18 can induce migration and cytotoxicity of NK cells from nonallergic donors, but had no effect on NK cells from allergic patients. The defect in CCL18 response by NK cells from allergic patients was not due to a binding issue between CCL18 and NK cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Allergy
Emily M. Mace
Summary: Human natural killer (NK) cells are innate lymphoid cells that play a crucial role in controlling viral infection and malignancy. They have the ability to distinguish self from nonself and eliminate virally infected and tumorigenic cells, making them a valuable tool for immunotherapy and disease fighting.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2023)
Review
Immunology
Umut Can Kucuksezer, Esin Aktas Cetin, Fehim Esen, Ilhan Tahrali, Nilgun Akdeniz, Metin Yusuf Gelmez, Gunnur Deniz
Summary: NK cells are a subset of innate lymphoid cells that play important roles in anti-tumor immune responses and immune regulation, with different subgroups showing cytotoxic functions or cytokine production. Their activation is influenced by a variety of factors, including cell surface receptors and cytokines, and their dysregulation can contribute to various immune-mediated diseases. Further research on NK cell biology and their potential therapeutic applications is necessary for better understanding and treatment of inflammatory disorders.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Dan Li, Yuande Wang, Meixiang Yang, Zhongjun Dong
Summary: The lack of mTOR kinase severely impairs NK cell development in mice. mTOR, Raptor, and Rictor play different roles in regulating NK cell development at different stages, with mTOR being essential for early NK cell differentiation.
CELL DEATH AND DIFFERENTIATION
(2021)
Review
Geriatrics & Gerontology
Le Zhang, Yingshuang Zhang, Dongsheng Fan
Summary: This review systematically evaluates the evidence on the functions of natural killer (NK) cells in Parkinson's disease (PD) and finds that alterations in the number of NK cells and cytotoxicity occur during PD progression. NK cells may play a neuroprotective role in PD pathogenesis, revealing potential novel targets for PD management and treatment.
FRONTIERS IN AGING NEUROSCIENCE
(2022)
Article
Immunology
Xinyi Yang, Desheng Weng, Qiuzhong Pan, Tong Xiang, Chaopin Yang, Zhengrong Wu, Minxing Li, Songzuo Xie, Yan Tang, Jianchuan Xia, Jingjing Zhao
Summary: This study investigated the use of adjuvant cellular immunotherapy in post-mastectomy breast cancer patients. The results showed that patients treated with cellular immunotherapy had a higher overall survival rate compared to those who did not receive the treatment, particularly those who received NK cell immunotherapy. Subgroup analyses also indicated that adjuvant cellular immunotherapy significantly improved the overall survival of patients with triple-negative breast cancer and those aged over 50 years.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Pediatrics
Egle Kvedaraite, Magda Lourda, HongYa Han, Bianca Tesi, Jenee Mitchell, Maja Idestrom, Natalia Mouratidou, George Rassidakis, Tatiana von Bahr Greenwood, Fleur Cohen-Aubart, Martin Jadersten, Selma Olsson Akefeldt, Mattias Svensson, George Kannourakis, Yenan T. Bryceson, Julien Haroche, Jan-Inge Henter
Summary: This study presented the first case series of patients with both Langerhans cell histiocytosis (LCH) and Crohn's disease (CD), highlighting diagnostic challenges and elevated IL-23 levels in LCH patients, with a correlation between lesional LCH cells and circulating IL-23 levels. Both CD and LCH should be considered in patients with inflammatory gastrointestinal involvement, with the IL-23 pathway being a common immunological trait between these two granulomatous diseases.
Article
Rheumatology
AnnaCarin Horne, Tatiana von Bahr Greenwood, Samuel C. C. Chiang, Marie Meeths, Caroline Bjorklund, Maria Ekelund, Peter Erensjo, Stefan Berg, Stefan Hagelberg, Yenan T. Bryceson, Ulf Andersson, Jan-Inge Henter
Summary: Moderately dosed etoposide demonstrated effectiveness in treating severe MAS-HLH, with all children responding well and surviving at latest follow-up. Some children showed improvement in neurological symptoms after treatment.
JOURNAL OF RHEUMATOLOGY
(2021)
Letter
Allergy
Andri Lemarquis, Tessa Campbell, Maribel Aranda-Guillen, Viktoria Hennings, Petter Brodin, Olle Kampe, Kaj Blennow, Henrik Zetterberg, Christine Wenneras, Kristina Eriksson, Nils Landegren, Yenan Bryceson, Stefan Berg, Olov Ekwall
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2021)
Review
Immunology
Vanessa Sancho-Shimizu, Petter Brodin, Aurelie Cobat, Catherine M. Biggs, Julie Toubiana, Carrie L. Lucas, Sarah E. Henrickson, Alexandre Belot, Stuart G. Tangye, Joshua D. Milner, Michael Levin, Laurent Abel, Dusan Bogunovic, Jean-Laurent Casanova, Shen-Ying Zhang
Summary: MIS-C, a newly emerging syndrome in children associated with COVID-19, shows heterogeneity resembling KD, possibly triggered by viruses and potentially linked to rare inborn errors of immunity altering the immune response. Discovery of monogenic IEIs underlying MIS-C may pave the way for a new genetic approach to classic KD.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Review
Pediatrics
Marie Meeths, Yenan T. Bryceson
Summary: HLH is a life-threatening hyperinflammatory syndrome with genetic predisposition and associations with variants in genes related to metabolism or immunity. Molecular insights have provided fundamental knowledge of the immune system, deepening our understanding of hyperinflammatory diseases and highlighting new treatment strategies.
Article
Immunology
Paul Bastard, Adrian Gervais, Tom Le Voyer, Jeremie Rosain, Quentin Philippot, Jeremy Manry, Eleftherios Michailidis, Hans-Heinrich Hoffmann, Shohei Eto, Marina Garcia-Prat, Lucy Bizien, Alba Parra-Martinez, Rui Yang, Liis Haljasmagi, Melanie Migaud, Karita Sarekannu, Julia Maslovskaja, Nicolas de Prost, Yacine Tandjaoui-Lambiotte, Charles-Edouard Luyt, Blanca Amador-Borrero, Alexandre Gaudet, Julien Poissy, Pascal Morel, Pascale Richard, Fabrice Cognasse, Jesus Troya, Sophie Trouillet-Assant, Alexandre Belot, Kahina Saker, Pierre Garcon, Jacques G. Riviere, Jean-Christophe Lagier, Stephanie Gentile, Lindsey B. Rosen, Elana Shaw, Tomohiro Morio, Junko Tanaka, David Dalmau, Pierre-Louis Tharaux, Damien Sene, Alain Stepanian, Bruno Megarbane, Vasiliki Triantafyllia, Arnaud Fekkar, James R. Heath, Jose Luis Franco, Juan-Manuel Anaya, Jordi Sole-Violan, Luisa Imberti, Andrea Biondi, Paolo Bonfanti, Riccardo Castagnoli, Ottavia M. Delmonte, Yu Zhang, Andrew L. Snow, Steven M. Holland, Catherine M. Biggs, Marcela Moncada-Velez, Andres Augusto Arias, Lazaro Lorenzo, Soraya Boucherit, Boubacar Coulibaly, Dany Anglicheau, Anna M. Planas, Filomeen Haerynck, Sotirija Duvlis, Robert L. Nussbaum, Tayfun Ozcelik, Sevgi Keles, Ahmed A. Bousfiha, Jalila El Bakkouri, Carolina Ramirez-Santana, Stephane Paul, Qiang Pan-Hammarstrom, Lennart Hammarstrom, Annabelle Dupont, Alina Kurolap, Christine N. Metz, Alessandro Aiuti, Giorgio Casari, Vito Lampasona, Fabio Ciceri, Lucila A. Barreiros, Elena Dominguez-Garrido, Mateus Vidigal, Mayana Zatz, Diederik van de Beek, Sabina Sahanic, Ivan Tancevski, Yurii Stepanovskyy, Oksana Boyarchuk, Yoko Nukui, Miyuki Tsumura, Loreto Vidaur, Stuart G. Tangye, Sonia Burrel, Darragh Duffy, Lluis Quintana-Murci, Adam Klocperk, Nelli Y. Kann, Anna Shcherbina, Yu-Lung Lau, Daniel Leung, Matthieu Coulongeat, Julien Marlet, Rutger Koning, Luis Felipe Reyes, Angelique Chauvineau-Grenier, Fabienne Venet, Guillaume Monneret, Michel C. Nussenzweig, Romain Arrestier, Idris Boudhabhay, Hagit Baris-Feldman, David Hagin, Joost Wauters, Isabelle Meyts, Adam H. Dyer, Sean P. Kennelly, Nollaig M. Bourke, Rabih Halwani, Narjes Saheb Sharif-Askari, Karim Dorgham, Jerome Sallette, Souad Mehlal Sedkaoui, Suzan AlKhater, Raul Rigo-Bonnin, Francisco Morandeira, Lucie Roussel, Donald C. Vinh, Sisse Rye Ostrowski, Antonio Condino-Neto, Carolina Prando, Anastasiia Bondarenko, Andras N. Spaan, Laurent Gilardin, Jacques Fellay, Stanislas Lyonnet, Kaya Bilguvar, Richard P. Lifton, Shrikant Mane, Mark S. Anderson, Bertrand Boisson, Vivien Beziat, Shen-Ying Zhang, Evangelos Andreakos, Olivier Hermine, Aurora Pujol, Part Peterson, Trine H. Mogensen, Lee Rowen, James Mond, Stephanie Debette, Xavier de Lamballerie, Xavier Duval, France Mentre, Marie Zins, Pere Soler-Palacin, Roger Colobran, Guy Gorochov, Xavier Solanich, Sophie Susen, Javier Martinez-Picado, Didier Raoult, Marc Vasse, Peter K. Gregersen, Lorenzo Piemonti, Carlos Rodriguez-Gallego, Luigi D. Notarangelo, Helen C. Su, Kai Kisand, Satoshi Okada, Anne Puel, Emmanuelle Jouanguy, Charles M. Rice, Pierre Tiberghien, Qian Zhang, Aurelie Cobat, Laurent Abel, Jean-Laurent Casanova
Summary: Autoantibodies neutralizing interferons are present in a significant percentage of critical COVID-19 patients, especially in older individuals, and their prevalence increases with age.
SCIENCE IMMUNOLOGY
(2021)
Article
Immunology
Takaki Asano, Bertrand Boisson, Fanny Onodi, Daniela Matuozzo, Marcela Moncada-Velez, Majistor Raj Luxman Maglorius Renkilaraj, Peng Zhang, Laurent Meertens, Alexandre Bolze, Marie Materna, Sarantis Korniotis, Adrian Gervais, Estelle Talouarn, Benedetta Bigio, Yoann Seeleuthner, Kaya Bilguvar, Yu Zhang, Anna-Lena Neehus, Masato Ogishi, Simon J. Pelham, Tom Le Voyer, Jeremie Rosain, Quentin Philippot, Pere Soler-Palacin, Roger Colobran, Andrea Martin-Nalda, Jacques G. Riviere, Yacine Tandjaoui-Lambiotte, Khalil Chaibi, Mohammad Shahrooei, Ilad Alavi Darazam, Nasrin Alipour Olyaei, Davood Mansouri, Figen Palabiyik, Tayfun Ozcelik, Giuseppe Novelli, Antonio Novelli, Giorgio Casari, Alessandro Aiuti, Paola Carrera, Simone Bondesan, Federica Barzaghi, Patrizia Rovere-Querini, Cristina Tresoldi, Jose Luis Franco, Julian Rojas, Luis Felipe Reyes, Ingrid G. Bustos, Andres Augusto Arias, Guillaume Morelle, Christele Kyheng, Jesus Troya, Laura Planas-Serra, Agatha Schluter, Marta Gut, Aurora Pujol, Luis M. Allende, Carlos Rodriguez-Gallego, Carlos Flores, Oscar Cabrera-Marante, Daniel E. Pleguezuelo, Rebeca Perez de Diego, Sevgi Keles, Gokhan Aytekin, Ozge Metin Akcan, Yenan T. Bryceson, Peter Bergman, Petter Brodin, Daniel Smole, C. I. Edvard Smith, Anna-Carin Norlin, Tessa M. Campbell, Laura E. Covill, Lennart Hammarstrom, Qiang Pan-Hammarstrom, Hassan Abolhassani, Shrikant Mane, Nico Marr, Manar Ata, Fatima Al Ali, Taushif Khan, Andras N. Spaan, Clifton L. Dalgard, Paolo Bonfanti, Andrea Biondi, Sarah Tubiana, Charles Burdet, Robert Nussbaum, Amanda Kahn-Kirby, Andrew L. Snow, Jacinta Bustamante, Anne Puel, Stephanie Boisson-Dupuis, Shen-Ying Zhang, Vivien Beziat, Richard P. Lifton, Paul Bastard, Luigi D. Notarangelo, Laurent Abel, Helen C. Su, Emmanuelle Jouanguy, Ali Amara, Vassili Soumelis, Aurelie Cobat, Qian Zhang, Jean-Laurent Casanova
Summary: A study revealed that rare X-linked TLR7 variants were found in 16 unrelated male individuals with critical COVID-19 pneumonia out of a cohort of 1202 male patients. No such variants were detected in 331 asymptomatic or mildly infected male individuals.
SCIENCE IMMUNOLOGY
(2021)
Article
Immunology
Katarzyna Babol-Pokora, Magdalena Wolowiec, Katarzyna Popko, Aleksandra Jaworowska, Yenan T. Bryceson, Bianca Tesi, Jan-Inge Henter, Wojciech Mlynarski, Wanda Badowska, Walentyna Balwierz, Katarzyna Drabko, Krzysztof Kalwak, Lucyna Maciejka-Kemblowska, Anna Pieczonka, Grazyna Sobol-Milejska, Sylwia Koltan, Iwona Malinowska
Summary: This study investigated the molecular genetics and outcomes of pediatric patients with HLH in Poland, finding that familial HLH variants were common and Epstein-Barr virus was the most common trigger for secondary HLH. The overall survival rate of patients was 74% with a median follow-up of 3.6 years.
ARCHIVUM IMMUNOLOGIAE ET THERAPIAE EXPERIMENTALIS
(2021)
Letter
Oncology
Audrone Muleviciene, Takuya Sekine, Timo Zondag, Yenan T. Bryceson, Bianca Tesi, Jelena Rascon
PEDIATRIC BLOOD & CANCER
(2022)
Review
Immunology
Hannes Lindahl, Yenan T. Bryceson
Summary: The development of high-throughput sequencing has advanced the understanding of genotype-phenotype correlations in congenital diseases. Neuroinflammatory diseases, although rare, are increasingly recognized among inborn errors of immunity and can have a significant impact on patient care. This review focuses on the signs and symptoms of neuroinflammation associated with pathogenic variants in immune genes and proposes a subdivision based on underlying mechanisms.
FRONTIERS IN IMMUNOLOGY
(2022)
Editorial Material
Genetics & Heredity
Martin Paucar, Bianca Tesi, Saeed Eshtad, Caroline Eriksson, Farouk Hashim, Daniel Nilsson, Kaveh Pourhamidi, Eva Hellstrom-Lindberg, Yenan T. Bryceson, Per Svenningsson
NEUROLOGY-GENETICS
(2021)
Letter
Biochemistry & Molecular Biology
Petter Brodin, Giorgio Casari, Liam Townsend, Cliona O'Farrelly, Ivan Tancevski, Judith Loeffler-Ragg, Trine H. Mogensen, Jean Laurent Casanova
Review
Immunology
Carl Inge Edvard Smith, Rula Zain, Anders osterborg, Marzia Palma, Marcus Buggert, Peter Bergman, Yenan Bryceson
Summary: The scarcity of plasmacytoid dendritic cells (pDCs) in patients with chronic lymphocytic leukaemia (CLL) may contribute to the severe clinical course of COVID-19 in these patients. Treatment of CLL with Bruton's tyrosine kinase (BTK) inhibitors can increase the number of pDCs.
SCANDINAVIAN JOURNAL OF IMMUNOLOGY
(2022)
Article
Immunology
Tessa Mollie Campbell, Zhiyong Liu, Qian Zhang, Marcela Moncada-Velez, Laura E. Covill, Peng Zhang, Ilad Alavi Darazam, Paul Bastard, Lucy Bizien, Giorgia Bucciol, Sara Lind Enoksson, Emmanuelle Jouanguy, Semsi Nur Karabela, Taushif Khan, Yasemin Kendir-Demirkol, Andres Augusto Arias, Davood Mansouri, Per Marits, Nico Marr, Isabelle Migeotte, Leen Moens, Tayfun Ozcelik, Isabelle Pellier, Anton Sendel, Sevtap Senoglu, Mohammad Shahrooei, C. I. Edvard Smith, Isabelle Vandernoot, Karen Willekens, Kadriye Kart Yasar, Peter Bergman, Laurent Abel, Aurelie Cobat, Jean-Laurent Casanova, Isabelle Meyts, Yenan T. Bryceson
Summary: IRF7-deficient individuals are prone to viral infections of the respiratory tract but are otherwise healthy, potentially due to residual IFN-beta and compensatory adaptive immunity.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Article
Immunology
Qian Zhang, Daniela Matuozzo, Jeremie Le Pen, Danyel Lee, Leen Moens, Takaki Asano, Jonathan Bohlen, Zhiyong Liu, Marcela Moncada-Velez, Yasemin Kendir-Demirkol, Huie Jing, Lucy Bizien, Astrid Marchal, Hassan Abolhassani, Selket Delafontaine, Giorgia Bucciol, Gulsum Ical Bayhan, Sevgi Keles, Ayca Kiykim, Selda Hancerli, Filomeen Haerynck, Benoit Florkin, Nevin Hatipoglu, Tayfun Ozcelik, Guillaume Morelle, Mayana Zatz, Lisa F. P. Ng, David Chien Lye, Barnaby Edward Young, Yee-Sin Leo, Clifton L. Dalgard, Richard P. Lifton, Laurent Renia, Isabelle Meyts, Emmanuelle Jouanguy, Lennart Hammarstrom, Qiang Pan-Hammarstrom, Bertrand Boisson, Paul Bastard, Helen C. Su, Stephanie Boisson-Dupuis, Laurent Abel, Charles M. Rice, Shen-Ying Zhang, Aurelie Cobat, Jean-Laurent Casanova
Summary: In an international cohort of 112 hospitalized children with COVID-19 pneumonia, 12 children with recessive inborn errors of type I interferon immunity were identified. These deficiencies may contribute to the development of COVID-19 pneumonia in children. Additionally, these deficiencies were not found in individuals without pneumonia from SARS-CoV-2 infection.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)