Article
Immunology
Jana-Julia Siegler, Margareta P. Correia, Tomas Hofman, Isabel Prager, Emrullah Birgin, Nuh N. Rahbari, Carsten Watzl, Ana Stojanovic, Adelheid Cerwenka
Summary: ILC3s are cytokine-producing lymphocytes that directly respond to tumor cells, leading to enhanced IFN-gamma release and TRAIL-dependent cytotoxicity against cancer cells. This suggests that ILC3s may play a role in anti-tumor immunity and could be further utilized for cancer therapies.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Laura Damele, Adriana Amaro, Alberto Serio, Silvia Luchetti, Ulrich Pfeffer, Maria Cristina Mingari, Chiara Vitale
Summary: EZH1/2 enzymes play a critical role in tumor development and hematopoiesis, with inhibitors potentially affecting NK cell differentiation and function. Clinical trials on EZH1/2 inhibitors against solid tumors are ongoing, but these inhibitors may also impact hematopoietic stem/progenitor cells and the generation of anti-tumor lymphocytes.
Article
Oncology
Michael J. Mauro, Timothy P. Hughes, Dong-Wook Kim, Delphine Rea, Jorge E. Cortes, Andreas Hochhaus, Koji Sasaki, Massimo Breccia, Moshe Talpaz, Oliver Ottmann, Hironobu Minami, Yeow Tee Goh, Daniel J. DeAngelo, Michael C. Heinrich, Valle Gomez-Garcia de Soria, Philipp le Coutre, Francois-Xavier Mahon, Jeroen J. W. M. Janssen, Michael Deininger, Naranie Shanmuganathan, Mark B. Geyer, Silvia Cacciatore, Fotis Polydoros, Nithya Agrawal, Matthias Hoch, Fabian Lang
Summary: Asciminib has been approved for patients with Philadelphia chromosome-positive chronic-phase chronic myeloid leukemia (CML-CP) who have received >= 2 prior tyrosine kinase inhibitors or have the T315I mutation. A phase 1 trial evaluated the safety and efficacy of asciminib monotherapy in 115 CML-CP patients without T315I. After a median exposure of approximately 4 years, most patients remained on asciminib and achieved significant molecular responses.
Article
Pharmacology & Pharmacy
An-Ni Zhong, Yi Yin, Bing-Jie Tang, Lei Chen, Hong-Wei Shen, Zhi-Ping Tan, Wen-Qun Li, Qun He, Bao Sun, Yan Zhu, Jie Xiao, Zhi-Ping Jiang, Ping Xu
Summary: The study revealed that hsa_circ_0058493 was significantly overexpressed in PBMCs of CML patients and associated with poor clinical efficacy of imatinib. Silencing this circRNA significantly inhibited the development of imatinib-resistant CML cells, suggesting its potential as a therapeutic target.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Immunology
Remi Fiancette, Conor M. Finlay, Claire Willis, Sarah L. Bevington, Jake Soley, Sky T. H. Ng, Syed Murtuza Baker, Simon Andrews, Matthew R. Hepworth, David R. Withers
Summary: Fiancette et al. used inducible transcription factor deletion models in mature tissue-resident ILCs to uncover complementary and competing transcriptional networks determining ILC3 phenotype and functional capacity. The study demonstrated the importance of ROR gamma t and ROR alpha in maintaining optimal effector functions in ILC3s, with ROR alpha being sufficient for robust interleukin-22 production in LTi-like ILC3 subset but not in NCR(+) ILC3s. Further, continued ROR gamma t expression was essential to restrain type 1 immunity associated transcriptional networks in NCR+ ILC3s coexpressing T-bet.
Review
Oncology
Stephanie Sembill, Maria Ampatzidou, Sonali Chaudhury, Michael Dworzak, Krzysztof Kalwak, Axel Karow, Alexander Kiani, Manuela Krumbholz, Maaike Luesink, Nora Naumann-Bartsch, Barbara De Moerloose, Michael Osborn, Kirk R. Schultz, Petr Sedlacek, Fiorina Giona, Christian Michel Zwaan, Hiroyuki Shimada, Birgitta Versluijs, Frederic Millot, Nobuko Hijiya, Meinolf Suttorp, Markus Metzler
Summary: The treatment of chronic myeloid leukemia has improved with the use of tyrosine kinase inhibitors; however, the prognosis for CML in the blast phase remains poor and treatment options are limited. In order to provide consistent therapy for children and adolescents with this high-risk disease, an international panel of pediatric CML experts developed recommendations based on current literature and national standards.
Article
Multidisciplinary Sciences
Golnaz Ensieh Kazemi-Sefat, Mohammad Keramatipour, Mohammad Vaezi, Seyed Mohsen Razavi, Kaveh Kavousi, Amin Talebi, Shahrbanoo Rostami, Marjan Yaghmaei, Bahram Chahardouli, Saeed Talebi, Kazem Mousavizadeh
Summary: This study identified important genetic variants in patients with myeloid blast crisis chronic myeloid leukemia (CML) using integrated genomic sequencing. These variants affect genes involved in leukemia stem cell proliferation, self-renewal, and differentiation. RNA sequencing was used to confirm these variants. This approach provides insights into the pathophysiology of CML and may aid in its management.
SCIENTIFIC REPORTS
(2022)
Article
Radiology, Nuclear Medicine & Medical Imaging
Lena M. Mittlmeier, Andrei Todica, Franz-Josef Gildehaus, Marcus Unterrainer, Leonie Beyer, Matthias Brendel, Nathalie L. Albert, Stephan T. Ledderose, Franziska J. Vettermann, Melanie Schott, Severin Rodler, Julian Marcon, Harun Ilhan, Clemens C. Cyran, Christian G. Stief, Michael Staehler, Peter Bartenstein
Summary: Ga-68-EMP-100 PET/CT imaging in mRCC patients demonstrates distinctly elevated uptake with high individual differences, including both c-MET-positive and c-MET-negative lesions, warranting further studies on its clinical use as a biomarker.
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
(2022)
Article
Oncology
Sara Pepe, Emilia Scalzulli, Gioia Colafigli, Alessio Di Prima, Marco Mancini, Daniela Diverio, Roberto Latagliata, Maurizio Martelli, Robin Foa, Massimo Breccia
Summary: The study demonstrated the long-term efficacy of imatinib in patients with chronic myeloid leukemia after interferon failure, with a possibility of attempting treatment-free remission in patients who achieve sustained deep molecular response.
LEUKEMIA & LYMPHOMA
(2021)
Article
Oncology
Fabien Muselli, Lucas Mourgues, Rita Morcos, Nathalie Rochet, Marielle Nebout, Agnes Guerci-Bresler, Douglas Faller, Robert M. William, Rana Mhaidly, Els Verhoeyen, Laurence Legros, Jean-Francois Peyron, Didier Mary
Summary: Although TKIs have shown clinical efficacy in treating CML, resistance and side effects remain major challenges. Targeting the PKC delta pathway to eliminate LSCs represents a potential new therapeutic approach. Studies have shown that PKC delta inhibition enhances the apoptotic response of CML cells to TKIs, indicating a synergistic effect in eradicating leukemic stem cells.
Article
Engineering, Biomedical
Qiang Qiu, Linyu Yang, Yunyu Feng, Zejiang Zhu, Ning Li, Li Zheng, Yuanyuan Sun, Cong Pan, Huandi Qiu, Xue Cui, Wei He, Fang Wang, Yuyao Yi, Minghai Tang, Zhuang Yang, Yunfan Yang, Zhihui Li, Lijuan Chen, Yiguo Hu
Summary: Purinostat Mesylate (PM) is a highly selective and active HDAC I/IIb inhibitor. The injectable formulation of PM (PMF) with cyclodextrin can overcome PM's poor solubility and improve its stability and pharmacokinetic properties. PM effectively represses the survival of leukemia cells and PMF significantly prevents CML progression by targeting leukemia stem cells (LSCs).
BIOACTIVE MATERIALS
(2023)
Article
Hematology
Wing-Yan Leung, Daniel Ka-Leung Cheuk, Frankie Wai-Tsoi Cheng, Alex Wing-Kwan Leung, Ka-Ho Chiu, Karin Kar-Huen Ho, Chak-Ho Li, Godfrey Chi-Fung Chan
Summary: We evaluated the feasibility of existing risk assessment tools for chronic myeloid leukemia (CML) in children and assessed the treatment, survival, and response. The results showed higher survival rates in the TKI-treated group, but the existing risk assessment tools could not accurately predict survival and treatment outcomes. Further research is needed to modify the risk assessment tools for pediatric CML.
ANNALS OF HEMATOLOGY
(2022)
Review
Oncology
Tian Yu, Weiming Li, Tao Yu
Summary: The application of immunosuppressive agents and targeted drugs, particularly tyrosine kinase inhibitors (TKI), in the treatment of hematological tumors, has significantly improved the prognosis of patients with chronic myeloid leukemia (CML). However, the use of TKI has led to an increased risk of co-infections, such as hepatitis B and COVID-19, due to the inhibition of immune function. This review provides an overview of the pathogenesis and standardized management principles for CML patients with comorbid COVID-19 or hepatitis B, aiming to enhance clinicians' awareness of the risks and improve patient outcomes.
FRONTIERS IN ONCOLOGY
(2023)
Article
Education, Scientific Disciplines
Christian Niederwieser, Nicolaus Kroeger
Summary: Molecular therapy with tyrosine kinase inhibitors (TKIs) has significantly reduced the need for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in chronic myeloid leukemia (CML). Early HSCT is crucial for better outcomes, while patients in different stages require different treatment approaches.
HEMATOLOGY-AMERICAN SOCIETY OF HEMATOLOGY EDUCATION PROGRAM
(2022)
Article
Medicine, Research & Experimental
Mansi Shah, Harish Kumar, Shaowei Qiu, Hui Li, Mason Harris, Jianbo He, Ajay Abraham, David K. Crossman, Andrew Paterson, Robert S. Welner, Ravi Bhatia
Summary: In chronic myeloid leukemia (CML), LT-HSCs expressing low c-KIT levels are primitive, quiescent, and drug-resistant leukemia-initiating cells, representing a critical target for eliminating disease persistence.
Correction
Immunology
Nadia Caccamo, Gabriella Pietra, Lucy C. Sullivan, Andrew G. Brooks, Teresa Prezzemolo, Marco P. La Manna, Diana Di Liberto, Simone A. Joosten, Krista E. van Meijgaarden, Paola Di Carlo, Lucina Titone, Lorenzo Moretta, Maria C. Mingari, Tom H. M. Ottenhoff, Francesco Dieli
EUROPEAN JOURNAL OF IMMUNOLOGY
(2022)
Review
Immunology
Paola Vacca, Gabriella Pietra, Nicola Tumino, Enrico Munari, Maria Cristina Mingari, Lorenzo Moretta
FRONTIERS IN IMMUNOLOGY
(2020)
Article
Immunology
Andrea Pelosi, Claudia Alicata, Nicola Tumino, Tiziano Ingegnere, Fabrizio Loiacono, Maria Cristina Mingari, Lorenzo Moretta, Paola Vacca
FRONTIERS IN IMMUNOLOGY
(2020)
Review
Pharmacology & Pharmacy
F. R. Mariotti, L. Quatrini, E. Munari, P. Vacca, N. Tumino, G. Pietra, M. C. Mingari, L. Moretta
BRITISH JOURNAL OF PHARMACOLOGY
(2020)
Review
Biochemical Research Methods
Genny Del Zotto, Francesca Antonini, Silvia Pesce, Francesca Moretta, Lorenzo Moretta, Emanuela Marcenaro
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)
Review
Biochemistry & Molecular Biology
Simona Sivori, Daniela Pende, Linda Quatrini, Gabriella Pietra, Mariella Della Chiesa, Paola Vacca, Nicola Tumino, Francesca Moretta, Maria Cristina Mingari, Franco Locatelli, Lorenzo Moretta
Summary: Innate immune cells, especially NK cells, play an important role in tumor immunotherapy by controlling tumor growth and metastasis. Various approaches have been developed, such as using IL-15 to improve NK cell function and utilizing NK cell engagers to activate NK cells. Additionally, NK cells may express inhibitory checkpoints like PD-1, which can be targeted for therapeutic use against certain tumors.
MOLECULAR ASPECTS OF MEDICINE
(2021)
Article
Oncology
Laura Damele, Adriana Amaro, Alberto Serio, Silvia Luchetti, Ulrich Pfeffer, Maria Cristina Mingari, Chiara Vitale
Summary: EZH1/2 enzymes play a critical role in tumor development and hematopoiesis, with inhibitors potentially affecting NK cell differentiation and function. Clinical trials on EZH1/2 inhibitors against solid tumors are ongoing, but these inhibitors may also impact hematopoietic stem/progenitor cells and the generation of anti-tumor lymphocytes.
Review
Immunology
Nicoletta Caronni, Elisa Montaldo, Luca Mezzanzanica, Francesco Cilenti, Marco Genua, Renato Ostuni
Summary: The development of cancer is influenced by the tumor microenvironment, and advancements in single-cell analysis technologies have helped unravel the contributions of the immune system to cancer progression. Tumor-associated macrophages and neutrophils play crucial roles in disrupting immune homeostasis and providing therapeutic opportunities for reprogramming the tumor microenvironment.
IMMUNOLOGICAL REVIEWS
(2021)
Article
Immunology
Francesco Cilenti, Giulia Barbiera, Nicoletta Caronni, Dario Iodice, Elisa Montaldo, Simona Barresi, Eleonora Lusito, Vincenzo Cuzzola, Francesco Maria Vittoria, Luca Mezzanzanica, Paolo Miotto, Pietro Di Lucia, Dejan Lazarevic, Daniela Maria Cirillo, Matteo Iannacone, Marco Genua, Renato Ostuni
Summary: Tightly controlling inflammatory gene expression by antagonistic environmental signals is crucial for immune protection and tissue damage prevention. PGE(2) modulates macrophage activation and interferes with LPS-induced gene expression through targeting the MEF2A-ERK5 interaction, impacting IFN I induction.
Article
Ophthalmology
Stefano Barabino, Elisa Montaldo, Maria Cristina Mingari, Cosimo Mazzotta, Sebastiano Giuffrida, Maurizio Rolando
Summary: The study demonstrated that tapered doses of loteprednol etabonate effectively reduced dry eye symptoms and improved ocular surface inflammation, while maintaining intraocular pressure and best corrected visual acuity.
EUROPEAN JOURNAL OF OPHTHALMOLOGY
(2022)
Article
Immunology
Elisa Montaldo, Eleonora Lusito, Valentina Bianchessi, Nicoletta Caronni, Serena Scala, Luca Basso-Ricci, Carla Cantaffa, Alice Masserdotti, Mattia Barilaro, Simona Barresi, Marco Genua, Francesco Maria Vittoria, Giulia Barbiera, Dejan Lazarevic, Carlo Messina, Elisabetta Xue, Sarah Marktel, Cristina Tresoldi, Raffaella Milani, Paola Ronchi, Salvatore Gattillo, Luca Santoleri, Raffaella Di Micco, Andrea Ditadi, Giulio Belfiori, Francesca Aleotti, Matteo Maria Naldini, Bernhard Gentner, Elisa Gardiman, Nicola Tamassia, Marco Antonio Cassatella, Andres Hidalgo, Immanuel Kwok, Lai Guan Ng, Stefano Crippa, Massimo Falconi, Francesca Pettinella, Patrizia Scapini, Luigi Naldini, Fabio Ciceri, Alessandro Aiuti, Renato Ostuni
Summary: Recent studies have found that human neutrophils exhibit substantial function diversity. This study performs immunophenotyping and transcriptome analysis to characterize the heterogeneity of human neutrophils under steady state and stress-induced conditions. The researchers uncover an extreme diversity of human neutrophils in vivo, reflecting the rates of cell mobilization, differentiation, and exposure to environmental signals. The findings suggest that systematic characterization of neutrophil plasticity may lead to the discovery of clinically relevant biomarkers and the development of diagnostic and therapeutic tools.
Review
Oncology
Laura Damele, Grazia Maria Spaggiari, Monica Parodi, Maria Cristina Mingari, Massimo Vitale, Chiara Vitale
Summary: NK cells have established anti-tumor activity against hematological malignancies and their role in controlling solid tumor growth and metastasis generation is supported by many studies. However, the tumor microenvironment may influence NK cell function. In this context, umbilical cord blood (UCB) is an important source of NK cells and CD34(+) HSPCs, which can generate NK cells. UCB-derived NK cells are valuable for in vitro and preclinical analyses and have been used in clinical settings against hematological malignancies. This review summarizes the characteristics of UCB-derived NK cells and the in vitro models for their expansion, highlighting their importance in cancer immunotherapy protocols.