Article
Biochemical Research Methods
Xiaoming Zhong, Hongqun Liao, Shaowen Hu, Kaiyuan Luo, Huifang Zhu
Summary: The natural product adenanthin significantly promotes the expression of NKG2D ligands in hepatoma cells, improving the killing activity of NK cells against liver cancer cells. This study is the first to report the anti-cancer effects of adenanthin mediated by indirect activation of NK cells. Adenanthin may be used as a sensitizing agent for NK cells in tumor immunotherapy.
MOLECULAR AND CELLULAR PROBES
(2021)
Article
Immunology
Alessandra Zecca, Valeria Barili, Andrea Olivani, Elisabetta Biasini, Carolina Boni, Paola Fisicaro, Ilaria Montali, Camilla Tiezzi, Raffaele Dalla Valle, Carlo Ferrari, Elisabetta Cariani, Gabriele Missale
Summary: NK cell exhaustion in hepatocellular carcinoma (HCC) is associated with tumor progression and poor clinical outcome. The hostile tumor microenvironment leads to metabolic deregulation and functional defects of infiltrating NK cells. Targeting p38 kinase can restore the metabolic and functional impairments of HCC-infiltrating NK cells. These findings provide a basis for the development of a new immunotherapeutic strategy for HCC.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Geriatrics & Gerontology
Rongjiao Liu, Qizhi Luo, Weiguang Luo, Ling Wan, Quan Zhu, Xiangli Yin, Xiaofang Lu, Zixuan Song, Leiyan Wei, Zhiqing Xiang, Yizhou Zou
Summary: In this study, a soluble NKCAR was designed to trigger NK cell cytotoxicity by binding with the ligand MICA through the NKG2D receptor expressed on NK cells. The NKCAR showed bifunctional activity, recognizing both the CD20 antigen of target cells and the NKG2D receptor of NKL cells. The soluble NKCAR mediated the killing of CD20(+) Daudi cells in vitro, indicating its potential clinical application for killing target tumor cells.
Article
Immunology
Sofia Carreira-Santos, Nelson Lopez-Sejas, Marina Gonzalez-Sanchez, Eva Sanchez-Hernandez, Alejandra Pera, Fakhri Hassouneh, Esther Duran, Rafael Solana, Javier G. Casado, Raquel Tarazona
Summary: This study provides a deep phenotypic characterization of in vitro-expanded CIML NK cells. Moreover, the correlations found between NK cell receptors and degranulation capacity of CIML NK cells allowed the identification of several biomarkers that could be useful in clinical settings.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Cell Biology
Suresh Gopi Kalathil, Yasmin Thanavala
Summary: This article discusses the important roles of NK cells and T cells in liver immunity, as well as their functional abnormalities and their association with progression in HCC. Immune checkpoint inhibitors play a crucial role in intervening tumor development.
Review
Medicine, Research & Experimental
Junfeng Chu, Fengcai Gao, Meimei Yan, Shuang Zhao, Zheng Yan, Bian Shi, Yanyan Liu
Summary: This article summarizes the recent advances and clinical applications of natural killer (NK) cell immunotherapy, focusing on the biology and function of NK cells, different types of NK cell therapy, and clinical trials and future perspectives of NK cell therapy.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Review
Cell Biology
Jagoda Siemaszko, Aleksandra Marzec-Przyszlak, Katarzyna Bogunia-Kubik
Summary: Natural Killer (NK) cells are natural cytotoxic cells of the innate immune system that can recognize and attack transformed or infected cells through their NKG2D receptor, which has significant immunological functions and clinical relevance.
Article
Biochemistry & Molecular Biology
Nehal M. El-Deeb, Omar M. Ibrahim, Mahmoud A. Mohamed, Mohamed M. S. Farag, Ayman A. Farrag, M. R. El-Aassar
Summary: This study investigates the use of novel mushroom polysaccharides formulated in Alginate/kappa carrageenan microcapsules to activate gut resident natural killer cells (NK) for immunotherapeutic effect against colon cancer. The microcapsules demonstrate superior stability and controlled release, and when activated by human NK cells, exhibit significant cytotoxic effects on colon cancer cells leading to apoptosis. The molecular mechanism behind this effect involves down regulation of anti-apoptotic genes and up regulation of pro-apoptotic gene expression.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Review
Biochemistry & Molecular Biology
Mehmet Gunduz, Pinar Ataca Atilla, Erden Atilla
Summary: NK cell-mediated adoptive immunotherapy has gained attention in hematology field due to the advancing understanding of NK cell receptor structure, biology and function. Recent technological advancements in gene editing and CARs have enabled the generation of genetically modified NK cells to enhance anti-tumor efficacy.
Article
Immunology
Hui-yang Wu, Ke-xin Li, Wan-ying Pan, Meng-qi Guo, Dei-zhi Qiu, Yan-jie He, Yu-hua Li, Yu-xian Huang
Summary: The combination of Venetoclax and NK cells demonstrates a synergistic cytolysis effect on AML cells by activating the NKG2D/NKG2DL ligand-receptor pathway and involving the NFKB signaling pathway.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Emily Chiu, Martin Felices, Frank Cichocki, Zachary Davis, Hongbo Wang, Katie Tuninga, Daniel A. Vallera, Tom Lee, Ryan Bjordahl, Karl Johan Malmberg, Bahram Valamehr, Jeffrey S. Miller
Summary: The researchers developed an immune therapy called NKG2C-KE, which directs specific types of NK cells to attack leukemia cells. This method showed promising results in experiments and could potentially become a new treatment strategy for leukemia.
Article
Biochemistry & Molecular Biology
Xianwu Wang, Xi Luo, Yunpeng Tian, Ting Wu, Jian Weng, Zhu Li, Feng Ye, Xuefei Huang
Summary: The study demonstrates that functionalizing NK cells with cetuximab through metabolic glycoengineering enhances tumor targeting abilities and improves anticancer efficacy against KRAS mutant colon cancer cells.
ACS CHEMICAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Marta Kinga Lemieszek, Paulina Adamczyk, Iwona Komaniecka, Wojciech Rzeski, Michal Tomczyk, Adrian Wiater
Summary: Despite the progress of medicine, colorectal cancer remains a major cause of morbidity and mortality. This study explored the use of (1 -> 3)-alpha-D-glucooligosaccharides (GOSs) to enhance the anticancer effect of NK-92 cells, a type of natural killer cells, against colon cancer cells LS180 and HT-29. The results showed that GOSs significantly increased the cytotoxic activity of NK-92 cells, suggesting their potential use as adjuvants in colon cancer immunotherapy.
Article
Immunology
Eric Alves, Emily McLeish, Pilar Blancafort, Jerome D. D. Coudert, Silvana Gaudieri
Summary: The NKG2D receptor-ligand axis is essential for detecting cellular distress, damage, or transformation, with functional NKG2D ligands associated with tumor rejection and viral clearance. Many viruses and tumors evade NKG2D recognition, but CRISPR technology offers novel therapeutic opportunities to enhance and maximize NKG2D-mediated immunity.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Oncology
Florencia Secchiari, Sol Yanel Nunez, Jessica Mariel Sierra, Andrea Ziblat, Maria Victoria Regge, Ximena Lucia Raffo Iraolagoitia, Agustin Rovegno, Carlos Ameri, Fernando Pablo Secin, Nicolas Richards, Hernando Rios Pita, Gonzalo Vitagliano, Luis Rico, Mauro Mieggi, Florencia Frascheri, Nicolas Bonanno, Leandro Blas, Aldana Trotta, Adrian David Friedrich, Mercedes Beatriz Fuertes, Carolina Ines Domaica, Norberto Walter Zwirner
Summary: NKG2D is an important activating receptor of natural killer (NK) cells that recognizes multiple ligands, including MICA. This study found that MICA is overexpressed in renal cell carcinoma (RCC) and is associated with decreased overall survival in RCC patients. Both tumor cells and tumor-infiltrating leukocytes showed increased MICA expression, while peripheral blood NK cells exhibited downregulated NKG2D. Furthermore, these NKG2D-expressing tumor-infiltrating NK cells displayed functional impairment and altered metabolic fitness.
Article
Hematology
Johannes Bloehdorn, Julia Krzykalla, Karlheinz Holzmann, Andreas Gerhardinger, Billy Michael Chelliah Jebaraj, Jasmin Bahlo, Kathryn Humphrey, Eugen Tausch, Sandra Robrecht, Daniel Mertens, Christof Schneider, Kirsten Fischer, Michael Hallek, Hartmut Doehner, Axel Benner, Stephan Stilgenbauer
Summary: Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab has been found to induce long-term remissions in patients with chronic lymphocytic leukemia. By using gene expression profiling and other prognostic parameters, integrative models can be developed to identify patients who specifically benefit from this treatment.
Article
Oncology
Maria A. Garcia-Marquez, Martin Thelen, Sarah Reinke, Diandra Keller, Kerstin Wennhold, Jonas Lehmann, Johanna Veldman, Sven Borchmann, Andreas Rosenwald, Stephanie Sasse, Arjan Diepstra, Peter Borchmann, Andreas Engert, Wolfram Klapper, Michael Von Bergwelt-Baildon, Paul J. Broeckelmann, Hans A. Schloesser
Summary: In this study on classical Hodgkin lymphoma patients, it was found that the exhausted lymphocyte phenotype significantly decreased during first-line anti-PD1 treatment. Additionally, T-cell responses against tumor-associated antigens were observed in some patients, which could be important for immune monitoring and cellular therapy.
Editorial Material
Oncology
Jan-Michel Heger, Sven Borchmann
LEUKEMIA & LYMPHOMA
(2022)
Article
Hematology
Elena Izquierdo, Daniela Vorholt, Stuart Blakemore, Benedict Sackey, Janica L. Nolte, Verena Barbarino, Jan Schmitz, Nadine Nickel, Daniel Bachurski, Liudmila Lobastova, Milos Nikolic, Michael Michalik, Reinhild Brinker, Olaf Merkel, Marek Franitza, Theodoros Georgomanolis, Rene Neuhaus, Maximilian Koch, Niklas Nasada, Gero Knittel, Bjoern Chapuy, Nicole Ludwig, Eckart Meese, Lukas Frenzel, Hans Christian Reinhardt, Martin Peifer, Rocio Rebollido-Rios, Heiko Bruns, Marcus Krueger, Michael Hallek, Christian P. Pallasch
Summary: This study reveals that genetic alterations in the DNA damage response pathway are a common mechanism of resistance to chemoimmunotherapy in B-cell malignancies. Loss of TP53 inhibits macrophage phagocytic capacity and affects the release of extracellular vesicles (EVs) and PD-L1 expression, leading to resistance to chemoimmunotherapy. These findings highlight the importance of using checkpoint inhibition in the combination treatment of B-cell malignancies with TP53 loss.
Article
Health Care Sciences & Services
Michael Kusch, Hildegard Labouvie, Vera Schiewer, Natalie Talalaev, Jan C. Cwik, Sonja Bussmann, Lusine Vaganian, Alexander L. Gerlach, Antje Dresen, Natalia Cecon, Sandra Salm, Theresia Krieger, Holger Pfaff, Clarissa Lemmen, Lisa Derendorf, Stephanie Stock, Christina Samel, Anna Hagemeier, Martin Hellmich, Bernd Leicher, Gregor Hueltenschmidt, Jessica Swoboda, Peter Haas, Anna Arning, Andrea Goettel, Kathrin Schwickerath, Ullrich Graeven, Stefanie Houwaart, Hedy Kerek-Bodden, Steffen Krebs, Christiana Muth, Christina Hecker, Marcel Reiser, Cornelia Mauch, Jennifer Benner, Gerdamarie Schmidt, Christiane Karlowsky, Gisela Vimalanandan, Lukas Matyschik, Lars Galonska, Annette Francke, Karin Osborne, Ursula Nestle, Markus Baeumer, Kordula Schmitz, Juergen Wolf, Michael Hallek
Summary: Germany is developing, implementing, and evaluating a new model of psycho-oncological care that aims to provide care to all cancer patients based on their individual needs. This model is being continuously improved and evaluated by an independent institution. The project aims to improve cross-sectoral care for cancer patients in Germany and explore its potential for integration into the healthcare system.
BMC HEALTH SERVICES RESEARCH
(2022)
Article
Genetics & Heredity
Binyamin A. Knisbacher, Ziao Lin, Cynthia K. Hahn, Ferran Nadeu, Marti Duran-Ferrer, Kristen E. Stevenson, Eugen Tausch, Julio Delgado, Alex Barbera-Mourelle, Amaro Taylor-Weiner, Pablo Bousquets-Munoz, Ander Diaz-Navarro, Andrew Dunford, Shankara Anand, Helene Kretzmer, Jesus Gutierrez-Abril, Sara Lopez-Tamargo, Stacey M. Fernandes, Clare Sun, Mariela Sivina, Laura Z. Rassenti, Christof Schneider, Shuqiang Li, Laxmi Parida, Alexander Meissner, Francois Aguet, Jan A. Burger, Adrian Wiestner, Thomas J. Kipps, Jennifer R. Brown, Michael Hallek, Chip Stewart, Donna S. Neuberg, Jose Martin-Subero, Xose S. Puente, Stephan Stilgenbauer, Catherine J. Wu, Elias Campo, Gad Getz
Summary: This study identifies genetic drivers and molecular subtypes associated with clinical outcomes in chronic lymphocytic leukemia (CLL) through genomic, transcriptomic, and epigenomic analysis. The findings provide fresh insights into the oncogenesis and prognostication of CLL.
Review
Medicine, General & Internal
Michael Hallek, Axel Ockenfels, Daniel Wiesen
Summary: This article presents the findings of a selective literature review on the application of behavioral economics interventions to improve medical decision-making. It suggests that these interventions may help physicians make better decisions and enhance treatment outcomes, although more evidence on their long-term effects is needed.
DEUTSCHES ARZTEBLATT INTERNATIONAL
(2022)
Article
Oncology
Theophilos Tzaridis, Johannes Weller, Daniel Bachurski, Farhad Shakeri, Christina Schaub, Peter Hau, Andreas Buness, Uwe Schlegel, Joachim-Peter Steinbach, Clemens Seidel, Roland Goldbrunner, Niklas Schaefer, Robert J. Wechsler-Reya, Michael Hallek, Bjoern Scheffler, Martin Glas, Lothar Haeberle, Ulrich Herrlinger, Christoph Coch, Katrin S. Reiners, Gunther Hartmann
Summary: Evaluation of serum-derived extracellular vesicles (EVs) from glioblastoma patients reveals that the upregulation of CD29, CD44, CD81, C1QA, and histone H3 in serum EVs correlates with tumor progression, suggesting their potential as biomarkers.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Article
Oncology
Volker Arndt, Daniela Doege, Stefan Froehling, Peter Albers, Hana Alguel, Ralf Bargou, Carsten Bokemeyer, Martin Bornhaeuser, Christian H. Brandts, Peter Brossart, Sara Yvonne Brucker, Tim H. Bruemmendorf, Hartmut Doehner, Norbert Gattermann, Michael Hallek, Volker Heinemann, Ulrich Keilholz, Thomas Kindler, Cornelia von Levetzow, Florian Lordick, Ulf Peter Neumann, Christoph Peters, Dirk Schadendorf, Stephan Stilgenbauer, Thomas Zander, Daniel Zips, Delia Braun, Thomas Seufferlein, Gerd Nettekoven, Michael Baumann
Summary: The capacities of German Comprehensive Cancer Centers (CCCs) in various aspects of oncology care were significantly affected during the first 2 years of the COVID-19 pandemic. Follow-up, psycho-oncologic care, and tumor surgery were particularly impacted, along with other areas of multidisciplinary oncological care. This study highlights the importance of developing strategies to prevent similar limitations in the future.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Article
Hematology
Jorge Garcia Borrega, Boris Boell, Matthias Kochanek, Jan-Hendrik Naendrup, Florian Simon, Noelle Sieg, Michael Hallek, Peter Borchmann, Udo Holtick, Alexander Shimabukuro-Vornhagen, Dennis A. Eichenauer, Jan-Michel Heger
Summary: A retrospective analysis was conducted on patients admitted to the intensive care unit (ICU) during hospitalization for high-dose chemotherapy and autologous stem cell transplantation (ASCT). The study found that the overall outcome was favorable for these patients.
ANNALS OF HEMATOLOGY
(2023)
Article
Oncology
Nadine Kutsch, Emily Eva Holmes, Sandra Robrecht, Gudrun Schueler, Ursula Vehling-Kaiser, Thomas Decker, Sigrun Mueller-Hagen, Karin Heinisch, Sebastian Boettcher, Matthias Ritgen, Karl-Anton Kreuzer, Stephan Stilgenbauer, Anna Maria Fink, Kirsten Fischer, Barbara Eichhorst, Michael Hallek, Clemens-Martin Wendtner
LEUKEMIA & LYMPHOMA
(2023)
Article
Cell Biology
Alexandra Brahmer, Carsten Geiss, Andriani Lygeraki, Elmo Neuberger, Theophilos Tzaridis, Tinh Thi Nguyen, Felix Luessi, Anne Regnier-Vigouroux, Gunther Hartmann, Perikles Simon, Kristina Endres, Stefan Bittner, Katrin S. Reiners, Eva-Maria Kraemer-Albers
Summary: Extracellular vesicles (EVs) released by cells carry specific biomolecules that can be used as liquid-biopsy markers for diagnosing brain diseases. This study evaluated a flow cytometry platform called EV Neuro assay for identifying and characterizing CNS-derived EVs and disease-specific markers in complex samples. The study compared different sample materials and EV isolation methods and found distinct EV profiles in glioblastoma cell lines and human astrocytes. The intensity of EV markers increased with higher EV input. Analysis of blood samples from patients with brain diseases and healthy controls showed varying EV marker intensities between individuals. Data normalization improved the identification of disease-specific markers. The EV Neuro assay proved useful for profiling EVs in complex samples. However, larger sample cohorts and higher effect sizes are needed for more reliable results in biomarker studies. Nonetheless, this study confirmed the potential of the EV Neuro assay for discovering disease-associated EV markers and monitoring circulating EV profiles in CNS diseases.
CELL COMMUNICATION AND SIGNALING
(2023)
Article
Oncology
Ruth Fluemann, Julia Hansen, Benedikt W. Pelzer, Pascal Nieper, Tim Lohmann, Ilmars Kisis, Tobias Riet, Viktoria Kohlhas, Phuong-Hien Nguyen, Martin Peifer, Nima Abedpour, Graziella Bosco, Roman K. Thomas, Moritz Kochanek, Jacqueline Knufer, Lorenz Jonigkeit, Filippo Beleggia, Alessandra Holzem, Reinhard Buttner, Philipp Lohneis, Jorn Meinel, Monika Ortmann, Thorsten Persigehl, Michael Hallek, Dinis Pedro Calado, Markus Chmielewski, Sebastian Klein, Joachim R. Goethert, Bjoern Chapuy, Branko Zevnik, F. Thomas Wunderlich, Bastian von Tresckow, Ron D. Jachimowicz, Ari M. Melnick, Hans Christian Reinhardt, Gero Knittel
Summary: Genomic profiling identified 5 subtypes of DLBCL, including the MCD/C5 cluster with MYD88, BCL2, PRDM1, and/or SPIB aberrations. Mouse models with B cell-specific Prdm1 or Spib aberrations were generated, showing molecular features of prememory and light-zone B cells. Combined BTK/BCL2 inhibition exhibited therapeutic activity in both mouse models and relapsed/refractory DLBCL patients.
BLOOD CANCER DISCOVERY
(2023)
Article
Medicine, General & Internal
L. Tometten, J. J. Malin, E. Pracht, P. J. Broeckelmann, C. Horn, R. Sprute, C. A. Langhorst, M. Hallek, G. Faetkenheuer, J. Rybniker
Summary: Immunodeficient patients with chronic and recurrent SARS-CoV-2 infections pose a significant health threat and present a major challenge in terms of treatment during the ongoing pandemic. Limited therapeutic options and emerging virus variants with immune escape mechanisms further complicate the medical care of these patients.
Article
Oncology
Othman Al-Sawaf, Michael Hallek, Kirsten Fischer
Summary: Minimal residual disease (MRD) has emerged as a sensitive and highly predictive surrogate marker for response to therapy in chronic lymphocytic leukemia (CLL). Various methods have been established for measuring and quantifying MRD, enabling the development of limited-duration therapies and exploration of MRD information in guiding treatment duration and determining sensitivity in prospective trials.
CLINICAL ADVANCES IN HEMATOLOGY & ONCOLOGY
(2022)
