Review
Immunology
Nina B. Horowitz, Imran Mohammad, Uriel Y. Moreno-Nieves, Ievgen Koliesnik, Quan Tran, John B. Sunwoo
Summary: Innate lymphoid cells (ILCs) play an important role in antitumor immunity, but their behavior in the context of cancer is not fully understood. Humanized mouse models serve as excellent tools for studying these pathways and interactions between ILCs and tumors.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Kentaro Yomogida, Tarin M. Bigley, Tihana Trsan, Susan Gilfillan, Marina Cella, Wayne M. Yokoyama, Takeshi Egawa, Marco Colonna
Summary: The study found that the expression of Hobit/Zfp683 is correlated with ILC1s and NK cells in a tissue- and context-dependent manner, with different effects on ILC1s and NK cells in different tissues. Hobit sustains liver ILC1 numbers while promoting the functional maturation of ILC1 in other tissues.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Oncology
Mireia Bachiller, Lorena Perez-Amill, Anthony Matthew Battram, Sebastian Ciro Carne, Amer Najjar, Els Verhoeyen, Manel Juan, Alvaro Urbano-Ispizua, Beatriz Martin-Antonio
Summary: This study demonstrates the important immunoregulatory role of CB-NK collaborating with CAR-T cells to enhance their antitumor activity. Combinatorial treatment based on CAR-T and CAR-NK cells or CB-NK and CAR-T cells showed that CB-NK required high doses for effectiveness, while a low number of CB-NK in the CAR-T product promoted early activation of CAR-T cells and enhanced anti-MM efficacy.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Review
Immunology
Rodolfo R. Favaro, Katherine Phillips, Romane Delaunay-Danguy, Kaja Ujcic, Udo R. Markert
Summary: Members of the innate immune system, specifically innate lymphoid cells (ILCs), play important roles in the uterine environment, supporting pregnancy and placental development. These cells demonstrate immune memory, allowing them to remember previously encountered antigens and mount enhanced responses. By studying ILCs, we can gain insights into the immunological mechanisms underlying female fertility/infertility, placental development, and distinct outcomes in second pregnancies.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Oisin Huhn, Xiaohui Zhao, Laura Esposito, Ashley Moffett, Francesco Colucci, Andrew M. Sharkey
Summary: Innate lymphoid cells (ILCs) are the most abundant immune cells in the uterine mucosa before and during pregnancy, with tissue-resident natural killer (NK) cells and ILCs being the main subsets. Recent advances in single-cell RNA sequencing and high dimensional flow and mass cytometry have significantly enhanced our understanding of the heterogeneity within the uILC compartment. These advancements may help answer key clinical questions regarding infertility, miscarriage, and pregnancy disorders related to uILC subsets.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Thuy T. Luu, Jonas Norskov Sondergaard, Lucia Pena-Perez, Shabnam Kharazi, Aleksandra Krstic, Stephan Meinke, Laurent Schmied, Nicolai Frengen, Yaser Heshmati, Marcin Kierczak, Thibault Bouderlique, Arnika Kathleen Wagner, Charlotte Gustafsson, Benedict J. Chambers, Adnane Achour, Claudia Kutter, Petter Hoglund, Robert Mansson, Nadir Kadri
Summary: FOXO1 and FOXO3 coordinately regulate essential developmental genes at multiple stages during murine NK cell and ILC lineage commitment through orchestrating distinct molecular mechanisms.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Alvaro Haroun-Izquierdo, Marianna Vincenti, Herman Netskar, Hanna van Ooijen, Bin Zhang, Laura Bendzick, Minoru Kanaya, Pouria Momayyezi, Shuo Li, Merete Thune Wiiger, Hanna Julie Hoel, Silje Zandstra Krokeide, Veronika Kremer, Geir Tjonnfjord, Stephanie Berggren, Kristina Wikstroem, Pontus Blomberg, Evren Alici, Martin Felices, Bjoern oenfelt, Petter Hoeglund, Bahram Valamehr, Hans-Gustaf Ljunggren, Andreas Bjoerklund, Quirin Hammer, Lise Kveberg, Frank Cichocki, Jeffrey S. Miller, Karl-Johan Malmberg, Ebba Sohlberg
Summary: This study demonstrates the feasibility of off-the-shelf therapy with a non-engineered, yet highly specific, NK cell population for hematological malignancies. The expanded adaptive NK cells retained high cytotoxicity and efficiently killed leukemia cells from AML patients.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Review
Oncology
Nicolas Jacquelot, Maryam Ghaedi, Kathrin Warner, Douglas C. Chung, Sarah Q. Crome, Pamela S. Ohashi
Summary: Immune checkpoints play a crucial role in regulating the immune system and are targeted in antibody-based therapies for improving T cell cytotoxic function in malignancies. These checkpoints are also expressed on innate lymphoid cells, leading to interest in understanding their function and potential for immunotherapy in anti-tumor immunity. Additional research focuses on the specificities and migration potential of ILC at different tissue sites, as well as strategies for modulating ILC as part of anti-cancer treatment.
Review
Immunology
Diana Coman, Isabelle Coales, Luke B. Roberts, Joana F. Neves
Summary: Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the intestine with a complex etiology involving genetics, gut microbiome, environment, and immune system. Recent research has suggested that innate lymphoid cells (ILCs) may play a significant role in the dysregulation of intestinal immunity observed in IBD. Despite being rare in the intestine, helper-like ILCs may contribute to the exacerbation of IBD pathology.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Rikang Wang, Weili Bao, Mouli Pal, Yunfeng Liu, Karina Yazdanbakhsh, Hui Zhong
Summary: This study identified the antimetastasis and pro-NK cell activity of IFN-IMo, identified FOXO1 as a key molecule for IFN-gamma driven monocyte differentiation and function, and found NR4A1 as an inhibitory molecule for IFN-IMo activity. It provided potential targets for developing superior monocytic cell therapy against cancer metastasis.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Cell Biology
Christopher S. Garris, Jeffrey L. Wong, Jeffrey Ravetch, David A. Knorr
Summary: This study demonstrates that CD40-expressing dendritic cells in the bladder tumor microenvironment can be targeted through intravesical delivery of CD40 agonist antibodies, leading to potent antitumor immune responses and reduction of exhausted CD8(+) T cells. These findings suggest a promising approach for the treatment of high-risk non-muscle-invasive bladder cancer.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Review
Oncology
Sainiteesh Maddineni, John L. Silberstein, John B. Sunwoo
Summary: This article reviews multiple approaches for allogeneic NK cell therapy and discusses the advantages and disadvantages of each method. In recent years, NK cells have become increasingly important players in the immune response against cancer.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Immunology
Dawid Swieboda, Thomas F. Rice, Yanping Guo, Simon Nadel, Ryan S. Thwaites, Peter J. M. Openshaw, Beth Holder, Fiona J. Culley
Summary: Early life is a vulnerable period for infectious diseases and allergy development. This study compares the abundance and function of different subpopulations of innate lymphocytes in cord blood and adult blood. The results show that NKT cells and mucosal-associated invariant T cells are less abundant in cord blood, while natural killer cells and other subsets of innate lymphocytes are similarly abundant. However, the functionality of NKT cells in cord blood, such as cytokine production and expression of granzyme B, is lower compared to adults. In contrast, cord blood natural killer cells and innate lymphoid cells are abundant and capable of producing their hallmark cytokines. These findings have important implications for early life immunity.
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
(2023)
Review
Immunology
Bernd Heinrich, Firouzeh Korangy
Summary: Innate lymphoid cells (ILCs) are a heterogeneous population of the innate immune system that play a crucial role in maintaining immune homeostasis. They exhibit high plasticity, allowing them to quickly respond to changes in their microenvironment. ILCs can transdifferentiate into different subsets in the tumor microenvironment, influencing the immune response and tumor therapy. This review summarizes the functional and plastic heterogeneity of ILCs in homeostasis and disease, with a focus on tumor-driven plasticity and the impact of ILC-induced inflammation on the tumor microenvironment and anti-tumor immunity.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Nicolas Jacquelot, Cyril Seillet, Fernando Souza-Fonseca-Guimaraes, Adrian G. Sacher, Gabrielle T. Belz, Pamela S. Ohashi
Summary: NK cells and ILC1 are specific innate lymphoid cell subsets crucial for detecting and eliminating pathogens and cancer cells. In the liver, they contribute to organ homeostasis through cytokine production and elimination of harmful microbes, with potential for targeted immunotherapies in hepatocellular carcinoma. Understanding the distinct roles and functions of these innate immune cells in liver cancer could lead to new treatment strategies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Hematology
Laura Surace, Jean-Marc Doisne, Pedro Escoll, Solenne Marie, Valerie Dardalhon, Carys Croft, Anna Thaller, Davide Topazio, Angelo Sparaneo, Antonia Cama, Olimpia Musumeci, Aurelio d'Ecclesia, Carmen Buchrieser, Naomi Taylor, James P. Di Santo
Summary: This study revealed that different subsets of NK cells exhibit varied responses in mitochondrial dynamics upon activation, highlighting the central role of mitochondrial polarization in regulating NK cell function.
Article
Multidisciplinary Sciences
Magali S. J. Dupont, Vincent Guillemot, Pascal Campagne, Nicolas Serafini, Solenne Marie, Xavier Montagutelli, James P. Di Santo, Christian A. J. Vosshenrich
Summary: The study demonstrates the diversity of NK cells in the Collaborative Cross and the identification of nine genomic loci driving phenotypic variations, showing the potential of CC as a resource to study NK cell diversity and its regulation by host genetics.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Editorial Material
Immunology
James Di Santo, Nadja Bakocevic
EUROPEAN JOURNAL OF IMMUNOLOGY
(2021)
Article
Immunology
Matthias Vanderkerken, Antonio P. Baptista, Marco De Giovanni, Satoshi Fukuyama, Robin Browaeys, Charlotte L. Scott, Paula S. Norris, Gerard Eberl, James P. Di Santo, Eric Vivier, Yvan Saeys, Hamida Hammad, Jason G. Cyster, Carl F. Ware, Alexei Tumanov, Carl De Trez, Bart N. Lambrecht
Summary: LT alpha(1)beta(2)-expressing Rorgt(+) ILC3s, together with B cells, control the splenic cDC niche size and the terminal differentiation of Sirp alpha(+)CD4(+)Esam(+) cDC2s. ILC3s play a critical role as perpetual regulators of lymphoid tissue homeostasis.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Editorial Material
Immunology
James Di Santo, Nadja Bakocevic
EUROPEAN JOURNAL OF IMMUNOLOGY
(2021)
Article
Immunology
Rui Yang, Marc Weisshaar, Federico Mele, Ibtihal Benhsaien, Karim Dorgham, Jing Han, Carys A. Croft, Samuele Notarbartolo, Jeremie Rosain, Paul Bastard, Anne Puel, Bernhard Fleckenstein, Laurie H. Glimcher, James P. Di Santo, Cindy S. Ma, Guy Gorochov, Aziz Bousfiha, Laurent Abel, Stuart G. Tangye, Jean-Laurent Casanova, Jacinta Bustamante, Federica Sallusto
Summary: This study presents a case of a child with MSMD, in which T-bet deficiency impairs IFN-gamma production by innate and innate-like adaptive cells, affecting the production of Th2 cytokines, particularly IL-5 and IL-13, leading to blood eosinophilia and UAI.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Immunology
Nikaia Smith, Pedro Goncalves, Bruno Charbit, Ludivine Grzelak, Maxime Beretta, Cyril Planchais, Timothee Bruel, Vincent Rouilly, Vincent Bondet, Jerome Hadjadj, Nader Yatim, Helene Pere, Sarah H. Merkling, Amine Ghozlane, Solen Kerneis, Frederic Rieux-Laucat, Benjamin Terrier, Olivier Schwartz, Hugo Mouquet, Darragh Duffy, James P. Di Santo
Summary: This study conducted a paired analysis of nasopharyngeal and systemic immune responses in COVID-19 patients, revealing distinct compartmentalization of immunity and shifts in the microbiome.
Article
Biochemistry & Molecular Biology
Marion Gransagne, Gabriel Ayme, Sebastien Brier, Gaelle Chauveau-Le Friec, Veronique Meriaux, Mireille Nowakowski, Francois Dejardin, Sylvain Levallois, Guilherme Dias de Melo, Flora Donati, Matthieu Prot, Sebastien Brule, Bertrand Raynal, Jacques Bellalou, Pedro Goncalves, Xavier Montagutelli, James P. Di Santo, Francoise Lazarini, Patrick England, Stephane Petres, Nicolas Escriou, Pierre Lafaye
Summary: This study developed a sandwich immunoassay to specifically detect the nucleoprotein (N) of SARS-CoV-2. Seven antibodies were identified that recognized the full N protein and did not cross react with nucleoproteins from common human coronaviruses. The antibodies mainly targeted conformational epitopes in the C-terminal or N-terminal domains and were able to detect SARS-CoV-2 variants.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Immunology
Elza Evren, Emma Ringqvist, Jean-Marc Doisne, Anna Thaller, Natalie Sleiers, Richard A. Flavell, James P. Di Santo, Tim Willinger
Summary: Evren et al. identify CD116(+) fetal liver cells as precursors of human alveolar macrophages in early life and reveal the impact of cell origin on lung macrophage identity and function.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Article
Medicine, General & Internal
Blandine Monel, Delphine Planas, Ludivine Grzelak, Nikaia Smith, Nicolas Robillard, Isabelle Staropoli, Pedro Goncalves, Francoise Porrot, Florence Guivel-Benhassine, Nathalie Demory Guinet, Julien Rodary, Julien Puech, Victor Euzen, Laurent Belec, Galdric Orvoen, Lea Nunes, Veronique Moulin, Jacques Fourgeaud, Maxime Wack, Sandrine Imbeaud, Pascal Campagne, Darragh Duffy, James P. Di Santo, Timothee Bruel, Helene Pere, David Veyer, Olivier Schwartz
Summary: The study found that the dynamics of shedding and immune responses of the SARS-CoV-2 alpha variant in the nasal mucosa are still poorly understood. Infectious virus can persist up to 14 days, but majority of individuals can carry infectious virus within two days of symptom onset, with this proportion decreasing over time. The presence of antibodies and cytokines can significantly affect viral load and viral decay.
Article
Multidisciplinary Sciences
Nicolas Serafini, Angelique Jarade, Laura Surace, Pedro Goncalves, Odile Sismeiro, Hugo Varet, Rachel Legendre, Jean-Yves Coppee, Olivier Disson, Scott K. Durum, Gad Frankel, James P. Di Santo
Summary: Group 3 innate lymphoid cells (ILC3s) in the intestine remain activated for months after exposure to Citrobacter rodentium, leading to enhanced immune response and defense capability. These trained ILC3s undergo metabolic changes and exhibit enhanced proliferative capacity and IL-22 production.
Review
Hematology
Laura Surace, James P. Di Santo
Summary: This review discusses the role of innate lymphoid cells (ILCs) as metabolic sentinels and how specific activities of ILC subsets influence homeostasis and disease. Recent studies have found that ILCs' metabolism, phenotype, and function are shaped by signals from the tissue microenvironment. ILCs have emerged as crucial sensors of metabolic stress.
CURRENT OPINION IN HEMATOLOGY
(2022)
Article
Multidisciplinary Sciences
Carys A. Croft, Anna Thaller, Solenne Marie, Jean-Marc Doisne, Laura Surace, Rui Yang, Anne Puel, Jacinta Bustamante, Jean-Laurent Casanova, James P. Di Santo
Summary: The Notch signaling pathway plays a crucial role in the development of innate lymphoid cells (ILCs) from human ILC precursors. The study identifies a Notch->RORC->IL-23R pathway that regulates ILC differentiation. These findings may have implications for expanding functional ILC subsets in vitro and developing novel ILC therapies for human diseases.
NATURE COMMUNICATIONS
(2022)
Article
Immunology
Angelique Jarade, Zacarias Garcia, Solenne Marie, Abdi Demera, Immo Prinz, Philippe Bousso, James P. Di Santo, Nicolas Serafini
Summary: Serafini and colleagues find that intestinal villus ILC3s acquire migratory 'patrolling' attributes and enhanced cytokine expression in response to inflammation. These findings reveal notable differences between ILC3s and T cells in immunosurveillance, with ILC3s showing adaptation towards mucosal immunosurveillance after inflammation.
Article
Medicine, Research & Experimental
Camille de Cevins, Marine Luka, Nikaia Smith, Sonia Meynier, Aude Magerus, Francesco Carbone, Victor Garcia-Paredes, Laura Barnabei, Maxime Batignes, Alexandre Boulle, Marie-Claude Stolzenberg, Brieuc P. Perot, Bruno Charbit, Tinhinane Fali, Vithura Pirabakaran, Boris Sorin, Quentin Riller, Ghaith Abdessalem, Maxime Beretta, Ludivine Grzelak, Pedro Goncalves, James P. Di Santo, Hugo Mouquet, Olivier Schwartz, Mohammed Zarhrate, Melanie Parisot, Christine Bole-Feysot, Cecile Masson, Nicolas Cagnard, Aurelien Corneau, Camille Brunaud, Shen-Ying Zhang, Jean-Laurent Casanova, Brigitte Bader-Meunier, Julien Haroche, Isabelle Melki, Mathie Lorrot, Mehdi Oualha, Florence Moulin, Damien Bonnet, Zahra Belhadjer, Marianne Leruez, Slimane Allali, Christele Gras-Leguen, Loic de Pontual, Alain Fischer, Darragh Duffy, Frederic Rieux-Laucat, Julie Toubiana, Mickael M. Menager
Summary: The study reveals that the most severe forms of multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 infection resulting in myocarditis are characterized by elevated levels of cytokines and chemokines, as well as a unique monocyte/dendritic cell gene signature correlated with sustained NF-κB activity and TNF-α signaling. This suggests a weak response to interferons, hyperinflammation, and increased response to oxidative stress related to HIF-1α and VEGF signaling.
