Review
Oncology
Jean Lemoine, Marco Ruella, Roch Houot
Summary: CAR T-cell therapy has emerged as a promising treatment for cancers, but a significant proportion of patients develop resistance to the treatment. Studies suggest that activation of apoptosis through death receptor signaling is a major mechanism of CAR T-cell cytotoxicity in vivo.
CLINICAL CANCER RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Lingtong Zhi, Meichen Yin, Xin Su, Zikang Zhang, Hui Lu, Mingfeng Li, Changjiang Guo, Zhiyuan Niu, Xuan Zhang, Wuling Zhu
Summary: Engineered natural killer (NK) cell-based therapies have shown broad potential in cancer treatment. The inhibitory pathway, however, remains a major obstacle. Researchers have designed a chimeric switch-receptor (CSR) PD1-DAP10-41BB to convert the inhibitory signal into a positive one. The CSR-expressing NK92 cells demonstrated enhanced cytotoxicity and suppressed tumor growth in mouse models. This study highlights the potential of engineered NK cells to treat a wide range of solid tumors.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Patrick A. Sandoz, Kyra Kuhnigk, Edina K. Szabo, Sarah Thunberg, Elina Erikson, Niklas Sandstroem, Quentin Verron, Andreas Brech, Carsten Watzl, Arnika K. Wagner, Evren Alici, Karl-Johan Malmberg, Michael Uhlin, Bjoern Oenfelt
Summary: Gamma delta T cells play a vital role in protecting against infections and tumors throughout life. Their cytotoxic functions are regulated by the availability of lytic molecules granzyme B and perforin. Live single-cell imaging provides new insights into the cytotoxic arsenal and functions of gamma delta T cells, which may aid in the development of more effective immunotherapies.
NATURE COMMUNICATIONS
(2023)
Review
Biochemistry & Molecular Biology
Zachary L. Z. Hay, Jill E. Slansky
Summary: This review discusses the mechanisms of action of granzymes released by cytotoxic T lymphocytes on target cells, particularly in the context of cancer and inflammatory diseases. The expression and function of granzymes are regulated by the environment and activation state, making them dynamic and responsive to individual circumstances.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Immunology
Yorleny Vicioso, Derek P. Wong, Nand K. Roy, Nayanika Das, Keman Zhang, Parameswaran Ramakrishnan, Reshmi Parameswaran
Summary: Germline deficiency of NF-kappa B c-Rel leads to a marked decrease in cytotoxic function of NK cells, which is regulated by c-Rel through controlling the expression of perforin and granzyme B. The study reveals a crucial role of c-Rel in the cytotoxic function of NK cells through transcriptional regulation of perforin and granzyme B expressions.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Medicine, Research & Experimental
Margaret Hallisey, Jenna Dennis, Elizabeth P. Gabriel, Alyssa Masciarelli, Jiajia Chen, Charlotte Abrecht, Martha Brainard, William M. Marcotte, Han Dong, Emma Hathaway, Mubin Tarannum, Juliana A. Vergara, Abigail N. Schork, Kevin Tyan, Giuseppe Tarantino, David Liu, Rizwan Romee, Osama E. Rahma, Mariano Severgnini, Stephen Hodi, Joanna Baginska
Summary: We developed a comprehensive method using mass cytometry to assess functional changes in immune populations and killing activity of peripheral blood mononuclear cells after cocultures with cancer cells. A 43-marker mass cytometry panel was applied to cocultures of immune cells from healthy donors with different cancer cell lines. This method enables discrimination of cancer cells from immune populations without specific cancer cell markers and simultaneous evaluation of phenotypical changes in both populations.
LABORATORY INVESTIGATION
(2023)
Article
Biotechnology & Applied Microbiology
Alessia Gravina, Grigol Tediashvili, Raja Rajalingam, Zoe Quandt, Chad Deisenroth, Sonja Schrepfer, Tobias Deuse
Summary: Engineered overexpression of CD64 protects cells from antibody-mediated killing, enhancing the efficacy of allogeneic cell therapeutics for cancer therapy or regenerative medicine.
NATURE BIOTECHNOLOGY
(2023)
Article
Immunology
Alexandros Karampatzakis, Petr Broz, Camille Rey, Bjorn Onfelt, Gabriela Dos Santos Cruz De Matos, Daniel Rycroft, Ashley Ambrose, Daniel M. Davis
Summary: The afucosylation of CD20 mAb increases NK cell cytotoxicity and IFN gamma secretion, as well as leading to faster killing of target cells and increased efficiency in serial killing by NK cells, due to the loss of CD16 causing disassembly of the immune synapse.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Christopher Bednar, Sabrina Kuebel, Arne Cordsmeier, Brigitte Scholz, Hanna Menschikowski, Armin Ensser
Summary: Granzyme B (GZMB) is an enzyme released by cytotoxic T lymphocytes and natural killer cells that induces apoptosis in target cells. A novel fluorogenic biosensor, CRSTAL, was designed to assess GZMB activity specifically and sensitively. CRSTAL showed strong and long-lasting fluorescence signal when activated by GZMB, making it a valuable tool in cancer immunotherapy for monitoring CAR-T cell activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Ranjan Upadhyay, Jonathan A. Boiarsky, Gvantsa Pantsulaia, Judit Svensson-Arvelund, Matthew J. Lin, Aleksandra Wroblewska, Sherry Bhalla, Nathalie Scholler, Adrian Bot, John M. Rossi, Norah Sadek, Samir Parekh, Alessandro Lagana, Alessia Baccarini, Miriam Merad, Brian D. Brown, Joshua D. Brody
Summary: The study revealed the crucial role of Fas-FasL in T cell killing of tumors and the bystander killing of antigen-negative tumor cells. This new finding may enhance the efficacy of immunotherapies and prevent cancer relapse by targeting both antigen expression and antigen-loss variants.
Article
Medicine, Research & Experimental
Marijana Vicic, Vlatka Sotosek, Ines Brajac, Marija Kastelan, Larisa Prpic-Massari
Summary: Lichen planus is a chronic mucocutanous disorder where cytotoxic lymphocytes attack basal keratinocytes leading to apoptosis. The article hypothesizes that granulysin molecule may play a crucial role in keratinocytes killing in lichen planus.
MEDICAL HYPOTHESES
(2021)
Article
Oncology
Katharina H. Susek, Ysabel A. Schwietzer, Maria Karvouni, Mari Gilljam, Marton Keszei, Alamdar Hussain, Johan Lund, Muhammad Kashif, Andreas Lundqvist, Hans-Gustaf Ljunggren, Hareth Nahi, Arnika K. Wagner, Evren Alici
Summary: This study designed novel NK cell specific PD1-based chimeric switch receptors, which enhance the anti-tumor activity of NK cells by modifying the PD1 structure, and demonstrated that this strategy has potential in PD-L1(+) tumor immunotherapy.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Article
Immunology
Miriam Aarsund, Tuula Anneli Nyman, Maria Ekman Stensland, Yunjie Wu, Marit Inngjerdingen
Summary: NK cells release extracellular vesicles (EVs) containing cytolytic proteins to target and kill cancer cells. A fractionation scheme enriched cytolytic NK-EVs, leading to the identification of distinct EV populations. Immunoaffinity pulldowns further enriched EVs containing cytolytic granule markers.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Seong-Eun Kim, Suji Yun, Junsang Doh
Summary: This study found that the extracellular matrix on the surface of solid tumor cells affects the cytotoxicity of immune cells. Solid tumor cells with high adhesion are more resistant to immune cell-mediated killing, while solid tumor cells with low adhesion are more easily killed by immune cells.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Vinicius O. Boldrini, Ana M. Marques, Raphael P. S. Quintiliano, Adriel S. Moraes, Carla R. A. V. Stella, Ana Leda F. Longhini, Irene Santos, Marilia Andrade, Breno Ferrari, Alfredo Damasceno, Rafael P. D. Carneiro, Carlos Otavio Brandao, Alessandro S. Farias, Leonilda M. B. Santos
Summary: This study found that CD19(+) B cells in the peripheral blood of multiple sclerosis (MS) patients may express serine-protease granzyme-B (GzmB), resembling cytotoxic CD8(+) T lymphocytes. This finding may provide important clues for investigating the pathogenesis of MS and for the development of new therapeutic interventions.
FRONTIERS IN IMMUNOLOGY
(2022)
Correction
Biotechnology & Applied Microbiology
Sergei Yakneen, Sebastian M. Waszak, Michael Gertz, Jan O. Korbel, Brice Aminou, Javier Bartolome, Keith A. Boroevich, Rich Boyce, Angela N. Brooks, Alex Buchanan, Ivo Buchhalter, Adam P. Butler, Niall J. Byrne, Andy Cafferkey, Peter J. Campbell, Zhaohong Chen, Sunghoon Cho, Wan Choi, Peter Clapham, Brandi N. Davis-Dusenbery, Francisco M. De La Vega, Jonas Demeulemeester, Michelle T. Dow, Lewis Jonathan Dursi, Juergen Eils, Roland Eils, Kyle Ellrott, Claudiu Farcas, Francesco Favero, Nodirjon Fayzullaev, Vincent Ferretti, Paul Flicek, Nuno A. Fonseca, Josep Ll. Gelpi, Gad Getz, Bob Gibson, Robert L. Grossman, Olivier Harismendy, Allison P. Heath, Michael C. Heinold, Julian M. Hess, Oliver Hofmann, Jongwhi H. Hong, Thomas J. Hudson, Barbara Hutter, Carolyn M. Hutter, Daniel Hubschmann, Seiya Imoto, Sinisa Ivkovic, Seung-Hyup Jeon, Wei Jiao, Jongsun Jung, Rolf Kabbe, Andre Kahles, Jules N. A. Kerssemakers, Hyung-Lae Kim, Hyunghwan Kim, Jihoon Kim, Youngwook Kim, Kortine Kleinheinz, Michael Koscher, Antonios Koures, Milena Kovacevic, Chris Lawerenz, Ignaty Leshchiner, Jia Liu, Dimitri Livitz, George L. Mihaiescu, Sanja Mijalkovic, Ana Mijalkovic Lazic, Satoru Miyano, Naoki Miyoshi, Hardeep K. Nahal-Bose, Hidewaki Nakagawa, Mia Nastic, Steven J. Newhouse, Jonathan Nicholson, Brian D. O'Connor, David Ocana, Kazuhiro Ohi, Lucila Ohno-Machado, Larsson Omberg, B. F. Francis Ouellette, Nagarajan Paramasivam, Marc D. Perry, Todd D. Pihl, Manuel Prinz, Montserrat Puiggros, Petar Radovic, Keiran M. Raine, Esther Rheinbay, Mara Rosenberg, Romina Royo, Gunnar Ratsch, Gordon Saksena, Matthias Schlesner, Solomon I. Shorser, Charles Short, Heidi J. Sofia, Jonathan Spring, Lincoln D. Stein, Adam J. Struck, Grace Tiao, Nebojsa Tijanic, David Torrents, Peter Van Loo, Miguel Vazquez, David Vicente, Jeremiah A. Wala, Zhining Wang, Sebastian M. Waszak, Joachim Weischenfeldt, Johannes Werner, Ashley Williams, Youngchoon Woo, Adam J. Wright, Qian Xiang, Liming Yang, Denis Yuen, Christina K. Yung, Junjun Zhang, Jan O. Korbel
NATURE BIOTECHNOLOGY
(2023)
Article
Health Care Sciences & Services
Patrick D. Gajewski, Stephan Getzmann, Peter Brode, Michael Burke, Cristina Cadenas, Silvia Capellino, Maren Claus, Erhan Genc, Klaus Golka, Jan G. Hengstler, Thomas Kleinsorge, Rosemarie Marchan, Michael A. Nitsche, Jorg Reinders, Christoph van Thriel, Carsten Watzl, Edmund Wascher
Summary: The Dortmund Vital Study aims to investigate the relationships between biological and environmental factors and cognitive functioning in healthy working adults. The study employs a combination of cross-sectional and longitudinal methods and collects a wide range of data, including demographics, psychology, behavior, cardiovascular health, and neuroimaging. The results of the study are expected to shed light on the individual differences in cognitive functioning with age and identify markers for healthy aging and cognitive decline.
JMIR RESEARCH PROTOCOLS
(2022)
Editorial Material
Immunology
Carsten Watzl
EUROPEAN JOURNAL OF IMMUNOLOGY
(2022)
Article
Immunology
Doris Urlaub, Natalie Wolfsdorff, Jan-Erik Hoffmann, Stefanie Dorok, Markus Hoffmann, Moritz Anft, Naomi Pieris, Patrick Guenther, Bernhard Schaaf, Uwe Cassens, Peter Broede, Maren Claus, Lea K. Picard, Sabine Wingert, Simone Backes, Deniz Durak, Nina Babel, Stefan Poehlmann, Frank Renken, Stefan Raunser, Carsten Watzl
Summary: Neutralizing antibodies against SARS-CoV-2 are found to be long-lasting and enhanced after vaccination in individuals who have recovered from COVID-19, providing clear benefits.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2022)
Article
Immunology
Anita Balazs, Pamela Millar-Buechner, Michael Muelleder, Vadim Farztdinov, Lukasz Szyrwiel, Annalisa Addante, Aditi Kuppe, Tihomir Rubil, Marika Drescher, Kathrin Seidel, Sebastian Stricker, Roland Eils, Irina Lehmann, Birgit Sawitzki, Jobst Roehmel, Markus Ralser, Marcus A. Mall
Summary: The nasal epithelium acts as the first line of defense against inhaled pathogens, allergens, and irritants, and plays a crucial role in the development of various respiratory diseases. This study aims to investigate the age-related differences in the structure and function of the nasal epithelium. The results showed intrinsic, age-related differences in the structure and function of the nasal epithelium, which may contribute to the development of age-dependent respiratory diseases.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Genetics & Heredity
Sebastian Tiesmeyer, Shashwat Sahay, Niklas Mueller-Boetticher, Roland Eils, Sebastian D. Mackowiak, Naveed Ishaque
Summary: The combination of a cell's transcriptional profile and location defines its function in a spatial context. Spatially resolved transcriptomics (SRT) has become a popular method for characterizing cells in situ. However, the correct aggregation of mRNA molecules into cells has been a computational problem in single-molecule SRT methods. SSAM-lite is an easy-to-use graphical interface tool that enables rapid and segmentation-free cell typing of SRT data in a web browser.
FRONTIERS IN GENETICS
(2022)
Article
Multidisciplinary Sciences
Philipp Klein, Stefan M. Kallenberger, Hanna Roth, Karsten Roth, Thi Bach Nga Ly-Hartig, Vera Magg, Janez Ales, Soheil Rastgou Talemi, Yu Qiang, Steffen Wolf, Olga Oleksiuk, Roma Kurilov, Barbara Di Ventura, Ralf Bartenschlager, Roland Eils, Karl Rohr, Fred A. Hamprecht, Thomas Hoefer, Oliver T. Fackler, Georg Stoecklin, Alessia Ruggieri
Summary: This study elucidated the molecular mechanism of stress granules formation by integrating quantitative experiments and mathematical modeling. The study revealed that the stress response is controlled by a stochastic switch, with key elements including cooperative activation of PKR, ultrasensitive response of SG formation to eIF2 alpha phosphorylation, and negative feedback via GADD34. Furthermore, the study identified GADD34 mRNA levels as a molecular memory of the ISR that plays a central role in cell adaptation to acute and chronic stress.
Article
Immunology
Lea Katharina Picard, Maren Claus, Frank Fasbender, Carsten Watzl
Summary: The engagement of CD56 can activate NK cells and induce degranulation, IFN-gamma secretion, and morphological changes, making CD56 a potential co-activating receptor in NK cells. This effect is dependent on cytokine stimulation and can be impaired by the inhibition of specific pathways. However, the absence of CD56 does not impact the cytotoxic activity of NK cells against tumor target cells.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2022)
Review
Cell Biology
Raghda A. Elsabbagh, Mona Rady, Carsten Watzl, Khaled Abou-Aisha, Mohamed Z. Gad
Summary: N6-methyl-adenosine (m(6)A) modification plays a crucial role in gene expression regulation and its dysregulation is associated with diseases. In the immune system, m(6)A modification regulates immune cell functions and immune responses.
CELL COMMUNICATION AND SIGNALING
(2022)
Article
Chemistry, Analytical
Nour Sharar, Konstantin Wuestefeld, Rahat Morad Talukder, Julija Skolnik, Katharina Kaufmann, Bernd Giebel, Verena Boerger, Friedrich Nolte, Carsten Watzl, Frank Weichert, Roland Hergenroeder, Victoria Shpacovitch
Summary: This study introduces a wide-field surface plasmon resonance microscopy sensor that utilizes the surface plasmon resonance phenomenon to detect biological and non-biological nanoparticles. The sensor is able to detect and quantify biological nanoparticles without the need for labeling, using target-specific antibodies. The research also includes modifications to the optical sensor system and evaluates their effectiveness.
Article
Health Care Sciences & Services
Patrick D. Gajewski, Jennifer A. Rieker, Georgios Athanassiou, Peter Broede, Maren Claus, Klaus Golka, Jan G. Hengstler, Thomas Kleinsorge, Michael A. Nitsche, Joerg Reinders, Anita Tisch, Carsten Watzl, Edmund Wascher, Stephan Getzmann
Summary: As employees age, their physical and mental abilities decline, which decreases their work ability and increases the risk for long-term sick leave or premature retirement. This study systematically evaluated a wide range of factors to identify the most crucial predictors of low and high work ability. The results showed that sociodemographic factors such as education, social activities, and sleep quality have a significant impact on work ability, and age-dependent and age-independent determinants of work ability were identified.
JMIR FORMATIVE RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Peter Broede, Maren Claus, Patrick D. Gajewski, Stephan Getzmann, Edmund Wascher, Carsten Watzl
Summary: The definition of immunological aging type requires establishing reference intervals for immunosenescence biomarkers based on age distribution. We determined the comprehensive immune age index IMMAX for 1605 individuals and identified age-specific centiles, allowing categorization of individuals as immunologically slow or fast aging types. The IMMAX was rescaled to equivalent years of life (EYOL) using the 50th percentile as a reference, and the immunological age gap was calculated as the difference between EYOL and chronological age.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Letter
Urology & Nephrology
Arturo Blazquez-Navarro, Lisa Mittmann, Constantin Joachim Thieme, Moritz Anft, Krystallenia Paniskaki, Adrian Doevelaar, Felix Sebastian Seibert, Bodo Hoelzer, Margarete Justine Konik, Marc Moritz Berger, Thorsten Brenner, Clemens Tempfer, Carsten Watzl, Toni Luise Meister, Stephanie Pfaender, Eike Steinmann, Sebastian Dolff, Ulf Dittmer, Oliver Witzke, Ulrik Stervbo, Toralf Roch, Michal Or-Guil, Timm Henning Westhoff, Nina Babel
JOURNAL OF NEPHROLOGY
(2023)