Article
Oncology
Qiuqiu Zhang, Qianwei Zhang, Huiyuan Li, Xiaofei Zhao, Han Zhang
Summary: Choroidal melanoma is commonly found in adults and lithium chloride has been shown to induce apoptosis in leukemia cells. In this study, lithium chloride was found to inhibit cell survival and clonogenic potential, induce apoptosis, and reduce proliferation of choroidal melanoma cells both in vitro and in vivo. The upregulation of NOXA and downregulation of Mcl-1 were identified as key factors in lithium chloride-induced apoptosis.
CANCER CELL INTERNATIONAL
(2021)
Article
Cell Biology
Jingyi Zhang, Yuetong Wang, Chujie Yin, Ping Gong, Zhenwei Zhang, Linxiang Zhao, Samuel Waxman, Yongkui Jing
Summary: This study proposes a new triple combination for the treatment of AML by targeting the Noxa/Mcl-1/Bim axis to reverse the Mcl-1/p-Chk1 resistance of cytarabine therapy, using artesunate as a bridge to enhance the effects of venetoclax and cytarabine.
CELL DEATH & DISEASE
(2022)
Article
Multidisciplinary Sciences
Mariana Belen Vera, Olivia Morris-Hanon, German Ignacio Nogueiras, Luisina Belen Ripari, Myrian Ines Esquivel, Carolina Perez-Castro, Leonardo Romorini, Gustavo Emilio Sevlever, Maria Elida Scassa, Guillermo Agustin Videla-Richardson
Summary: The recurrence of Glioblastoma is partly caused by resistant glioma stem cells. In this study, Bcl-xL and Mcl-1 were found to be crucial in regulating patient-derived glioma stem cell survival. Combining Bcl-xL inhibitors with chemotherapeutic agents can lead to increased cell death, and the sensitivity to Bcl-xL inhibition is correlated with Noxa expression levels.
SCIENTIFIC REPORTS
(2022)
Article
Oncology
Shady I. Tantawy, Aloke Sarkar, Stefan Hubner, Zhi Tan, William G. Wierda, Abdelraouf Eldeib, Shuxing Zhang, Steven Kornblau, Varsha Gandhi
Summary: This study aims to investigate the mechanism of MCL-1i-induced Mcl-1 protein stability. Both in vivo and in vitro experiments demonstrate that MCL-1i-induced Mcl-1 protein stability is mainly associated with defective Mcl-1 ubiquitination and concurrent apoptosis induction. Additionally, MCL-1i also enhances Mcl-1Thr163 phosphorylation via ERK pathway, contributing to Mcl-1 stability.
CLINICAL CANCER RESEARCH
(2023)
Article
Cell Biology
Flore Sneyers, Martijn Kerkhofs, Femke Speelman-Rooms, Kirsten Welkenhuyzen, Rita La Rovere, Ahmed Shemy, Arnout Voet, Guy Eelen, Mieke Dewerchin, Stephen W. G. Tait, Bart Ghesquiere, Martin D. Bootman, Geert Bultynck
Summary: Intracellular Ca2+ signals play a crucial role in various cellular processes. Research has shown that BAPTAi can induce apoptosis in cancer cells by inhibiting mTORC1 activity and impairing glycolysis, independent of Ca2+ signaling. Additionally, direct inhibition of PFKFB3 emerges as a potential therapeutic target in MCL-1-dependent cancers.
CELL DEATH & DISEASE
(2023)
Article
Oncology
Dante S. Bortone, Mark G. Woodcock, Joel S. Parker, Benjamin G. Vincent
Summary: T-cell receptor (TCR) repertoire profiling is important in cancer immunology and immunotherapy, with diversity being a key statistic. A study found undersampling to be a major source of bias in diversity estimates, and a model was developed to improve the accuracy of diversity estimates, which could enhance predictions of patient responses to immunotherapy.
CANCER IMMUNOLOGY RESEARCH
(2021)
Review
Pharmacology & Pharmacy
Omar Al-Odat, Max von Suskil, Robert Chitren, Weam Elbezanti, Sandeep Srivastava, Tulin Budak-Alpddogan, Subash Jonnalagadda, Bharat Aggarwal, Manoj Pandey
Summary: Mcl-1 protein plays a critical role in the progression of multiple myeloma and inhibiting this protein is considered a therapeutic strategy. Remarkable advancements have been made in the development of selective Mcl-1 inhibitors, which can be used as single agents or in combination therapy.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Oncology
Haolan Wang, Ming Guo, Hudie Wei, Yongheng Chen
Summary: MCL-1, an antiapoptotic protein, is frequently overexpressed in many tumor types and closely associated with tumorigenesis, poor prognosis, and drug resistance. Its central role in regulating the mitochondrial apoptotic pathway makes it an attractive target for cancer therapy. Progress has been made towards MCL-1 inhibitors and some have entered clinical trials.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2021)
Article
Chemistry, Organic
Patrick B. Brady, Bryan K. Sorensen, Roberto M. Risi, Michael L. Curtin, Robert A. Mantei, Alan S. Florjancic, Anthony Mastracchio, Cheng Ji, Aaron R. Kunzer, Chunqiu Lai, Gregory E. Storer, Vincent S. Chan, Rodger F. Henry, Andrew J. Souers, Michael R. Michaelides, Andrew S. Judd, T. Matthew Hansen
Summary: We describe the synthesis of ABBV-467 on a decagram scale, enabling preclinical characterization. The strategy is convergent and stereoselective.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Cell Biology
Ming Li, Feng Gao, Xiaoying Li, Yu Gan, Shuangze Han, Xinfang Yu, Haidan Liu, Wei Li
Summary: The E3 ligase TRAF4 is closely related to radioresistance in oral squamous cell carcinoma (OSCC) by stabilizing MCL-1 through Akt signaling. Targeting TRAF4 may be a promising strategy to overcome radioresistance in OSCC.
CELL DEATH & DISEASE
(2022)
Article
Hematology
Meghan E. Turnis, Ewa Kaminska, Kaitlyn H. Smith, Brittany J. Kartchner, Peter Vogel, Jonathan D. Laxton, Richard A. Ashmun, Paul A. Ney, Joseph T. Opferman
Summary: Deletion of erythroid-specific Mcl1 results in embryonic lethality due to severe anemia caused by lack of mature red blood cells. MCL-1 is required only during early definitive erythropoiesis, with developing erythrocytes becoming MCL-1 independent and upregulating BCL-xL expression during later stages.
Article
Cell Biology
Sandra Weller, Astrid Toenniessen, Benjamin Schaefer, Tobias Beigl, Alina Muenchow, Kathrin Bopple, Ute Hofmann, Bernhard F. Gillissen, Walter E. Aulitzky, Hans-Georg Kopp, Frank Essmann
Summary: The BCL-2 inhibitor ABT-199 enhances its anti-tumor effect by blocking BCL-2 and inhibiting MCL-1 through the activation of NOXA. This finding suggests the potential of combining ABT-199 with other drugs for improved cancer treatment.
CELL DEATH DISCOVERY
(2022)
Review
Biochemistry & Molecular Biology
Pooja Mittal, Sujata Singh, Rajesh Sinha, Anju Shrivastava, Archana Singh, Indrakant Kumar Singh
Summary: MCL-1 plays a crucial role in cancer cells and its overexpression is associated with drug resistance. Advancements in selective MCL-1 inhibitors offer new therapeutic strategies for cancer treatment.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Biochemistry & Molecular Biology
Kaixin Wu, Seon-Min Woo, Seung-Un Seo, Taeg-Kyu Kwon
Summary: BMI-1, a polycomb ring finger oncogene, is highly expressed in multiple cancer cells and plays a role in cancer cell proliferation, invasion, and apoptosis. Inhibition of BMI-1 leads to Mcl-1 destabilization by downregulating DUB3, ultimately inducing cancer cell death. This study demonstrates the importance of BMI-1 in cancer stemness and the potential therapeutic implications of targeting BMI-1 in cancer treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Cell Biology
Hui San Chin, Nai Yang Fu
Summary: The protein Mcl-1 plays a crucial role in cell survival, with its essential functions revealed through genetically engineered mouse models. Understanding its physiological roles in different tissues and developmental stages has implications for the treatment of various diseases, including cancer.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Editorial Material
Immunology
Klaas P. J. M. van Gisbergen, Joke M. M. den Haan
CELLULAR & MOLECULAR IMMUNOLOGY
(2022)
Article
Endocrinology & Metabolism
Inga Kavazovic, Mia Krapic, Ammarina Beumer-Chuwonpad, Bojan Polic, Tamara Turk Wensveen, Niels A. Lemmermann, Klaas P. J. M. van Gisbergen, Felix M. Wensveen
Summary: Type 2 diabetes leads to impaired antiviral and anticancer capacity of memory CD8 T cells due to hyperglycemia, rather than hyperinsulinemia, in the context of obesity.
Article
Immunology
Natasja A. M. Kragten, Renske L. R. E. Taggenbrock, Loreto Parga Vidal, Rene A. W. van Lier, Regina Stark, Klaas P. J. M. van Gisbergen
Summary: iNKT cells have developmental potential after lineage commitment, and they differentiate into resident memory cells similar to tissue-resident memory T cells. The transcription factors Hobit and Blimp-1 play a crucial role in the development of iNKT cells, specifically in the differentiation of central memory iNKT cells into resident memory iNKT cells.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2022)
Review
Urology & Nephrology
Loreto Parga-Vidal, Michiel C. van Aalderen, Regina Stark, Klaas P. J. M. van Gisbergen
Summary: The discovery of tissue-resident memory T (T-RM) cells residing in peripheral tissues at key pathogen entry sites has revolutionized our understanding of T cell memory responses. These cells can promptly respond to infections without the need for migration, proliferation or differentiation. They form isolated populations in peripheral tissues and play a crucial role in combating infections and tumor growth.
NATURE REVIEWS NEPHROLOGY
(2022)
Article
Immunology
Loreto Parga-Vidal, Renske L. R. E. Taggenbrock, Ammarina Beumer-Chuwonpad, Hajar Aglmous, Natasja A. M. Kragten, Felix M. Behr, Astrid A. Bovens, Rene A. W. van Lier, Regina Stark, Klaas P. J. M. van Gisbergen
Summary: Tissue-resident memory T cells (Trm) are retained in peripheral tissues after infection for enhanced protection against secondary encounter with the same pathogen. In this study, the transcription factors Hobit and Blimp-1 were found to play important roles in the formation and tissue retention of Trm.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2022)
Article
Immunology
Dora Gasparini, Inga Kavazovic, Igor Barkovic, Vitomir Maricic, Viktor Ivanis, Dijana Travica Samsa, Viktor Persic, Bojan Polic, Tamara Turk Wensveen, Felix M. Wensveen
Summary: This study investigated the impact of freediving on the immune system and found that cytotoxic immune cells transiently change their functional profile to restrict tissue damage after freediving.
IMMUNOLOGY LETTERS
(2022)
Article
Multidisciplinary Sciences
Iris N. Pardieck, Tetje C. van der Sluis, Esme T. van der Gracht, Dominique M. B. Veerkamp, Felix M. Behr, Suzanne van Duikeren, Guillaume Beyrend, Jasper Rip, Reza Nadafi, Elham Beyranvand Nejad, Nils Mulling, Dena J. Brasem, Marcel G. M. Camps, Sebenzile K. Myeni, Peter J. Bredenbeek, Marjolein Kikkert, Yeonsu Kim, Luka Cicin-Sain, Tamim Abdelaal, Klaas P. J. M. van Gisbergen, Kees L. M. C. Franken, Jan Wouter Drijfhout, Cornelis J. M. Melief, Gerben C. M. Zondag, Ferry Ossendorp, Ramon Arens
Summary: Repeated booster vaccinations with a three dose regimen of a synthetic peptide vaccine significantly enhance the CD8(+) T cell response, leading to protection against lethal SARS-CoV-2 infection. Understanding the mechanisms and impact of booster vaccinations is crucial for vaccine design and delivery.
NATURE COMMUNICATIONS
(2022)
Review
Immunology
Renske L. R. E. Taggenbrock, Klaas P. J. M. van Gisbergen
Summary: This review discusses the recent advances in the development, differentiation, and effector maturation of ILC1s, as well as the observed heterogeneity in ILC1 populations within different tissues. The study of transcriptional programs reveals the shared characteristics between ILC1s and other tissue-resident lymphocytes, aiding in the effective response of ILC1s to tissue-invading pathogens.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2023)
Editorial Material
Immunology
Klaas P. J. M. van Gisbergen, Carmen Gerlach
Summary: The expansion capacity of naive T cells is believed to be the main factor determining the magnitude of CD8 T-cell responses against intracellular pathogens. However, a study challenges this notion and reveals that the recruitment of naive T-cell clones into primary responses can be incomplete, especially when there are low-affinity interactions between the T-cell receptor and the pathogen's antigen. This research shows that the regulation of CD8 T-cell response size involves control at the level of recruitment and expansion of naive CD8 T cells.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2023)
Article
Immunology
Ammarina Beumer-Chuwonpad, Floris P. J. van Alphen, Natasja A. M. Kragten, Julian J. Freen-van Heeren, Maria Rodriguez Gomez, Arthur J. Verhoeven, Maartje van den Biggelaar, Klaas P. J. M. van Gisbergen
Summary: Reduced oxygen pressure alters the metabolism of CD8(+) T cells, enhancing their granzyme B and IFN-gamma production capacity, but not affecting their expansion potential. In vivo, memory CD8(+) T cells cultured under low oxygen pressure provide protection against rechallenge.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Ante Benic, Sanja Mikasinovic, Felix M. M. Wensveen, Bojan Polic
Summary: In their pursuit of health, people often adopt extreme diets, but the acute impact of these diets on the liver is not well understood. A study on mice found that a high protein diet (HPD) led to liver damage, with an increase in liver enzymes and the formation of necrotic lesions. The activation of macrophages and neutrophils was observed, and the depletion of neutrophils prevented liver inflammation. Prolonged HPD feeding resulted in an increase of anti-inflammatory mediators, suggesting a protective response. In conclusion, extreme diets may not have a major impact on the liver within two weeks, but diets with high protein content should be avoided to prevent severe acute liver damage.
Review
Pharmacology & Pharmacy
Cheng-Chih Hsiao, Els Vos, Klaas P. J. M. van Gisbergen, Jorg Hamann
Summary: GPR56/ADGRG1 is an adhesion G protein-coupled receptor with significant roles in brain development, haematopoiesis, male fertility, and tumorigenesis. Recent studies have shown that GPR56 is also present in human cytotoxic NK and T cells, where its expression is driven by the transcription factor HOBIT and associated with cytolytic mediators, CX(3)CR1 and CD57. It indicates a state of terminal differentiation and cellular exhaustion, and disappears upon cellular activation. Functional studies reveal that GPR56 regulates cell migration and effector functions, acting as an inhibitory immune checkpoint. This article discusses the current understanding of GPR56 in cytotoxic lymphocytes.
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
(2023)
Article
Cell Biology
Inga Kavazovi, Christoforos Dimitropoulos, Dora Gasparini, Marina Roncevic Filipovic, Igor Barkovic, Jan Koster, Niels A. Lemmermann, Marina Babic, DurCica Cekinovi Grbesa, Felix M. Wensveen
Summary: Memory CD8 T cells play an important role in protection against breakthrough infections with SARS-CoV-2. The route of antigen exposure impacts the functional capacity of these cells. Vaccination results in a narrower T cell receptor usage scope compared to infection alone or in combination with vaccination. Infected individuals with memory CD8 T cells secrete less TNF compared to vaccinated individuals, but this difference is negated if infected individuals have also been vaccinated. Our findings provide insights into susceptibility to re-infection after different routes of SARS-CoV-2 antigen exposure.
Article
Immunology
Jet van den Dijssel, Ruth R. Hagen, Rivka de Jongh, Maurice Steenhuis, Theo Rispens, Dionne M. Geerdes, Juk Yee Mok, Angela H. M. Kragten, Mariel C. Duurland, Niels J. M. Verstegen, S. Marieke van Ham, Wim Je van Esch, Klaas Pjm van Gisbergen, Pleun Hombrink, Anja ten Brinke, Carolien E. van de Sandt
Summary: This study identified a range of conserved SARS-CoV-2 CD8(+)T cell epitopes and determined their immunodominance and phenotypic profiles. The findings suggest that SARS-CoV-2 infection induces a predominant CD8(+)T memory response directed against a variety of conserved SARS-CoV-2 epitopes, which likely contributes to long-term protection against severe disease.
CLINICAL & TRANSLATIONAL IMMUNOLOGY
(2022)