Article
Immunology
Tiziano A. Schweizer, Srikanth Mairpady Shambat, Clement Vulin, Sylvia Hoeller, Claudio Acevedo, Markus Huemer, Alejandro Gomez-Mejia, Chun-Chi Chang, Jeruscha Baum, Sanne Hertegonne, Eva Hitz, Thomas C. Scheier, Daniel A. Hofmaenner, Philipp K. Buehler, Holger Moch, Reto A. Schuepbach, Silvio D. Brugger, Annelies S. Zinkernagel
Summary: The study found that in severely ill COVID-19 patients, neutrophils exhibit a necroptosis-sensitive phenotype, characterized by cell lysis, increased release of DAMPs, elevated RIPK1 levels, and involvement of MLKL. This necroptosis is induced by the TNFRI/TNF-alpha axis. Furthermore, reduced sFasL levels in COVID-19 patients directly increase RIPK1 levels, exacerbate TNF-induced necroptosis, and correlate with disease severity, which is abolished in patients treated with glucocorticoids.
CLINICAL & TRANSLATIONAL IMMUNOLOGY
(2021)
Article
Medicine, General & Internal
Haixu Yu, Wei Rong, Jie Yang, Jie Lu, Ke Ma, Zhuohui Liu, Hui Yuan, Lei Xu, Yulin Li, Zhi-Cheng Jing, Jie Du
Summary: This study found that reduced plasma TRAIL levels predict short-term adverse events in normotensive patients with acute PE. The combination of TRAIL and hs-cTnI as a biomarker-based risk stratification strategy has a similar risk classification effect in normotensive patients with acute PE.
JOURNAL OF CLINICAL MEDICINE
(2022)
Review
Medicine, General & Internal
David N. Zacks, Andrew J. Kocab, Joanne J. Choi, Meredith S. Gregory-Ksander, Marisol Cano, James T. Handa
Summary: This review summarizes the relationship between cell death pathways and the death of retinal pigment epithelial (RPE) and retinal cells in AMD, and discusses a novel approach of targeting the Fas receptor to preserve these structures.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Biotechnology & Applied Microbiology
Qiang Zhou, Jianxia Yuan, Yi Liu, Yayun Wu
Summary: Cisatracurium besilate inhibits gastric cancer cell proliferation, promotes apoptosis, increases the expression of p53 and PUMA, and enhances TRAIL-induced apoptosis. However, pifithrin-alpha can reverse the synergistic effects of cisatracurium besilate and TRAIL on AGS cell activities.
Review
Physiology
Laurel A. Grisanti
Summary: Cardiovascular disease is a leading cause of death globally. Cardiomyocyte death, which occurs in heart damage and stress, contributes to cardiac dysfunction and further damages the heart. Apoptosis, a regulated form of cell death, can occur through intrinsic or extrinsic pathways. The poorly characterized TNF-related ligand TRAIL and its receptors have been found to play a role in cardiac pathology. This article aims to provide an overview of the current understanding of TRAIL and its receptors in normal and pathological conditions in the heart.
FRONTIERS IN PHYSIOLOGY
(2023)
Article
Cell Biology
Emir Bozkurt, Heiko Dussmann, Manuela Salvucci, Brenton L. Cavanagh, Sandra Van Schaeybroeck, Daniel B. Longley, Seamus J. Martin, Jochen H. M. Prehn
Summary: The study reveals that TRAIL signaling not only activates apoptosis in colon cancer cells but also induces entosis through TRAIL receptors and the structural presence of caspase-8. The association of TRAIL signaling with cell-in-cell structures is significant in colorectal cancer, especially in the context of patient prognosis. Factors controlling entosis in tumors remain to be elucidated despite the evidence of entosis in cancers.
JOURNAL OF CELL BIOLOGY
(2021)
Review
Cell Biology
Gael Galli, Pierre Vacher, Bernhard Ryffel, Patrick Blanco, Patrick Legembre
Summary: The study of CD95-mediated signaling pathways is significant, and previous research has identified numerous factors involved. However, due to the dynamic nature of protein-protein interactions and their occurring in various cellular locations, it is difficult to predict the specific cellular outcomes associated with CD95 engagement. CD95 stimulation can lead to apoptosis, necroptosis, pyroptosis, or pro-inflammatory signaling pathways. Recent data suggests that CD95 may also activate pattern recognition receptors that sense damage-associated molecular patterns, potentially contributing to inflammation and cancer development or severity of chronic inflammatory and autoimmune disorders.
Article
Veterinary Sciences
Soo-Hyeon Kim, Byung-Joon Seung, Min-Kyung Bae, Ha-Young Lim, Seung-Hee Cho, Jung-Hyang Sur
Summary: The study found that in high-grade carcinomas, TRAIL protein expression was significantly decreased, while FADD and caspase-3 expression positively correlated with TRAIL expression. However, the apoptotic index in high-grade tumors paradoxically increased, suggesting that the loss of TRAIL along with dysregulation of TRAIL-induced extrinsic apoptotic pathway molecules could affect malignant progression of canine mammary tumors.
VETERINARY AND COMPARATIVE ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Xiaoming Li, Fang Li, Xixi Zhang, Haiwei Zhang, Qun Zhao, Ming Li, Xiaoxia Wu, Lingxia Wang, Jianling Liu, Xuanhui Wu, Yangjing Ou, Mingyan Xing, Yue Zhang, Jiangshan Deng, Xiuzhe Wang, Yan Luo, Jinbao Li, Yuwu Zhao, Haibing Zhang
Summary: This study reveals the important role of caspase-8 auto-cleavage in regulating necroptosis and maintaining lymphocyte homeostasis.
CELL DEATH AND DIFFERENTIATION
(2022)
Review
Immunology
Gabrielle Fredman, Sayeed Khan
Summary: The failure to resolve inflammation contributes to prevalent diseases like atherosclerosis, and there is an unmet clinical need to find ways to enhance resolution. Specialized pro-resolving mediators (SPMs) counteract pro-inflammatory pathways and promote tissue repair without compromising host defense. One major function of SPMs is to enhance the clearance of dead cells, and phagocytes, such as macrophages, play a crucial role in this process. This review highlights the role of SPMs in clearing apoptotic and necroptotic cells and suggests that targeting phagocytosis could provide new treatments for non-resolving diseases like atherosclerosis.
IMMUNOLOGICAL REVIEWS
(2023)
Review
Cell Biology
Haoying Wang, Mengxiao Liu, Xi Zeng, Ya Zheng, Yuping Wang, Yongning Zhou
Summary: This review summarizes the effects of various cell death modalities on gastric cancer cells and the tumor microenvironment, as well as the molecular mechanisms and regulatory pathways involved. It explores the prevalence and complexity of cell death in gastric cancer progression and highlights the potential of cell death-related therapies in gastric cancer treatment.
CELL DEATH DISCOVERY
(2022)
Article
Genetics & Heredity
Atsushi Watanabe, Kunio Miyake, Koshi Akahane, Kumiko Goi, Keiko Kagami, Hideo Yagita, Takeshi Inukai
Summary: Immunotherapies specific for BCP-ALL, such as anti-CD19 CAR T-cells and blinatumomab, have significantly improved outcomes in refractory cases. The methylation status of DR4 and DR5 genes is associated with gene expression levels, cell-surface expression, and TRAIL-sensitivities, suggesting potential clinical relevance in predicting immunotherapy efficacy. Evaluating methylation status of DR4 and DR5 genes may be informative in certain cases with unfavorable karyotypes.
Article
Critical Care Medicine
Hongseok Yoo, Jin Young Lee, Junseon Park, Gee Young Suh, Kyeongman Jeon
Summary: The study found that elevated levels of Fas ligand were associated with the severity and mortality of sepsis, but not correlated with RIPK3 levels.
Article
Cell Biology
Tayyab Shahzad, Cho-Ming Chao, Stefan Hadzic, Judith Behnke, Luisa Biebach, Eva Boettcher-Friebertshaeuser, Jochen Wilhelm, Anne Hilgendorff, Klaus-Peter Zimmer, Rory E. Morty, Saverio Bellusci, Harald Ehrhardt
Summary: Hyperoxia-induced inflammation and tissue damage are crucial steps leading to BPD. TRAIL plays a protective role in lung development, and its depletion leads to structural damage.
CELL DEATH & DISEASE
(2022)
Article
Oncology
Najib Ben Khaled, Katharina Hammer, Liangtao Ye, Ahmed Alnatsha, Sebastian A. Widholz, Ignazio Piseddu, Simon Sirtl, Julia Schneider, Stefan Munker, Ujjwal Mukund Mahajan, Juan Jose Montero, Joscha Griger, Julia Mayerle, Florian P. Reiter, Enrico N. De Toni
Summary: Research has identified frequent changes in BRCA genes in pancreatic cancer patients, especially in BRCA2. Pancreatic cancers with alterations in BRCA genes are sensitive to treatment with PARP inhibitors. This study shows that the combination of olaparib and TRAIL can be more effective than olaparib alone in killing pancreatic cancer cells. Furthermore, the combination of olaparib and TRAIL also kills cancer cells without BRCA2 mutations. These findings suggest a potential new combination therapy for pancreatic cancer independent of BRCA2 mutations.
Article
Hematology
Mark Gurney, Arwen Stikvoort, Emma Nolan, Lucy Kirkham-McCarthy, Stanislav Khoruzhenko, Rama Shivakumar, Sonja Zweegman, Niels W. C. J. Van de Donk, Tuna Mutis, Eva Szegezdi, Subhashis Sarkar, Michael O'Dwyer
Summary: There is strong biological rationale for combining alloeneic natural killer (NK) cell therapies with a chimeric antigen receptor (CAR) to improve the targeting of acute myeloid leukemia (AML). However, CD38 expression on NK cells and its induction during ex vivo NK cell expansion pose challenges to the development of a CD38 CAR-NK cell therapy. This study successfully used gene editing technology to reduce CD38 expression in expanded NK cells, resulting in reduced fratricide and enhanced targeting of primary AML cells. Additionally, pretreatment of AML cells with all-trans retinoic acid further augmented the cytotoxic potential of CD38 CAR-NK cells. These findings support the investigation of CD38 knockdown - CD38 CAR-NK cells as a promising immunotherapeutic approach for AML treatment.
Review
Oncology
Claire M. Robinson, Aaron Talty, Susan E. Logue, Katarzyna Mnich, Adrienne M. Gorman, Afshin Samali
Summary: Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer with poor treatment outcomes. A major challenge in PDAC treatment strategies is the dense stroma surrounding tumor cells, shielding them from treatment. The unfolded protein response (UPR) may play a role in the progression and therapy resistance of PDAC.
Review
Hematology
Eimear O'Reilly, Hojjat Alizadeh Zeinabad, Eva Szegezdi
Summary: Hematopoietic stem cells (HSC) are responsible for producing mature blood cells, with most HSCs being in a state of quiescence and controlled by intrinsic and extrinsic mechanisms. In acute myeloid leukemia (AML), leukemic cells take over the hematopoietic bone marrow niche, acquiring a quiescent state and resistance to chemotherapy. Efforts to target driver mutations in AML are progressing, but addressing drug resistance in quiescent leukemic stem cells (LSCs) remains a challenge.
Article
Cell Biology
Katarzyna Mnich, Izabela Koryga, Karolina Pakos-Zebrucka, Melissa Thomas, Susan E. Logue, Leif A. Eriksson, Adrienne M. Gorman, Afshin Samali
Summary: Stress-induced apoptosis is primarily mediated through the intrinsic pathway involving caspase-9. A protein complex termed the 'stressosome' containing ATG5-ATG12, FADD, and caspase-8 was found to be activated by various stress stimuli in caspase-9-deficient cells. However, only ER stress and heat shock led to stressosome-dependent cell death. In silico modeling proposed the structure of the stressosome complex, with FADD acting as an adaptor protein interacting with pro-caspase-8 and ATG5-ATG12.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2021)
Article
Multidisciplinary Sciences
Vincent Deruelle, Stephanie Bouillot, Viviana Job, Emmanuel Taillebourg, Marie-Odile Fauvarque, Ina Attree, Philippe Huber
Summary: The phospholipase ExoU from Pseudomonas aeruginosa acts on plasma membrane lipids in infected cells, causing membrane rupture and host cell necrosis. Once injected into the host cytoplasm, ExoU requires a host chaperone found on secretory vesicles to reach the plasma membrane and exert its phospholipase activity.
NATURE COMMUNICATIONS
(2021)
Article
Engineering, Biomedical
Naledi Shologu, Mehmet Gurdal, Eva Szegezdi, Una FitzGerald, Dimitrios I. Zeugolis
Summary: This study evaluated the potential of macromolecular crowding in improving cell-derived matrices for in vitro tumor models. NP40 was the most effective decellularisation protocol in removing cellular matter while preserving the deposited matrix. Macromolecular crowding derived matrices produced by mammary fibroblasts showed increased adhesion molecules, metalloproteinases, and proinflammatory cytokines, as well as enhanced resistance to doxorubicin and reduced cell death caused by reactive oxygen species.
Article
Oncology
D. Swan, R. Henderson, C. McEllistrim, S. D. Naicker, J. Quinn, M. R. Cahill, V. Mykytiv, E. Lenihan, E. Mulvaney, M. Nolan, I. Parker, A. Natoni, K. Lynch, A. E. Ryan, E. Szegezdi, J. Krawczyk, P. Murphy, M. O'Dwyer
Summary: The study investigated the combination of Daratumumab with cyclophosphamide, bortezomib, and dexamethasone for newly diagnosed multiple myeloma patients. The results showed high rates of complete response and a favorable progression-free survival rate, indicating the effectiveness of the treatment regimen.
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2022)
Letter
Cell Biology
Stuart Creedican, Claire M. Robinson, Katarzyna Mnich, Md Nahidul Islam, Eva Szegezdi, Ruth Clifford, Janusz Krawczyk, John B. Patterson, Stephen P. FitzGerald, Mark Summers, Ciaran Richardson, Kenneth Martin, Adrienne M. Gorman, Afshin Samali
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2022)
Article
Cell & Tissue Engineering
Mark Gurney, Eimear O'Reilly, Sarah Corcoran, Sarah Brophy, Janusz Krawczyk, Neil M. Otto, David L. Hermanson, Richard W. Childs, Eva Szegezdi, Michael E. O'Dwyer
Summary: This study reports a promising application of transposon engineering to donor-derived NK cells and emphasizes the importance of feeder-mediated NK cell activation and expansion in the current protocol. The approach enabled clinically relevant expansion of NK cells and expression of chimeric antigen receptor (CAR), and the CAR-NK cells effectively targeted AML cells expressing CLL-1. Additionally, the concurrent delivery of CRISPR/Cas9 cargo enhanced the cytotoxicity and altered the phenotype of NK cells by knockout of the NK cell cytokine checkpoint cytokine-inducible SH2-containing protein (CIS) gene.
Review
Oncology
Hojjat Alizadeh Zeinabad, Eva Szegezdi
Summary: TRAIL, as a promising anticancer drug with low toxicity, has not been successfully translated into a therapeutic molecule due to its short in vivo half-life and tumor cells' resistance. Nanotechnology shows potential to overcome these limitations and offers better solutions.
Meeting Abstract
Hematology
Hojjat Alizadeh Zeinabad, Wen Jie Yeoh, Philippe Krebs, Carsten Riether, Mihai Lomora, Yara Banz, Eva Szegezdi
Meeting Abstract
Hematology
Mark Gurney, Margaret Twohig, Derya Goksu Helvaci, Eimear O'Reilly, Sarah Brophy, Janusz Krawczyk, David L. Hermanson, Eva Szegezdi, Michael E. O'Dwyer
Article
Multidisciplinary Sciences
Sarah Ennis, Alessandra Conforte, Eimear O'Reilly, Javid Sabour Takanlu, Tatiana Cichocka, Sukhraj Pal Dhami, Pamela Nicholson, Philippe Krebs, Pilib O. Broin, Eva Szegezdi
Summary: In this study, a single-cell gene expression database of 339,381 bone marrow cells was established to comprehensively characterize the microenvironment of both healthy and acute myeloid leukemia (AML). Significant changes in cell type proportions and gene expression were observed in AML, indicating disruption of the entire niche. Predicted interactions between hematopoietic stem and progenitor cells (HSPCs) and other bone marrow cell types were also explored, revealing an expansion of interactions in AML that promote HSPC-cell adhesion, immunosuppression, and cytokine signaling. Transforming growth factor b1 (TGFB1)-related interactions were particularly widespread and were shown to drive AML cell quiescence in vitro. These findings highlight potential mechanisms of enhanced AML-HSPC competitiveness and a skewed microenvironment fostering AML growth.