Article
Immunology
Francoise Vuillier, Zhi Li, Iain Black, Melania Cruciani, Erminia Rubino, Frederique Michel, Sandra Pellegrini
Summary: This study reveals that miR-3614-5p, induced by IFN-I, represses ADAR1 and promotes the activation of innate sensors and the expression of IFN-beta and IL-6. These findings shed light on the role of miR-3614-5p in regulating dsRNA metabolism, cell homeostasis, and innate immunity.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Naama Margolis, Hanna Moalem, Tomer Meirson, Gilli Galore-Haskel, Ettai Markovits, Erez N. Baruch, Bella Vizel, Avner Yeffet, Julia Kanterman-Rifman, Assaf Debby, Michal J. Besser, Jacob Schachter, Gal Markel
Summary: The interaction between melanoma cells and T cells can enhance the chemotaxis of new T cells. ADAR1-p150 expression is correlated with immune infiltration and can be induced by immunotherapy. ADAR1 regulates T cell migration through the secretion of chemokines.
CANCER IMMUNOLOGY RESEARCH
(2022)
Review
Oncology
Jessica Thornton, Gagan Chhabra, Chandra K. Singh, Glorimar Guzman-Perez, Carl A. Shirley, Nihal Ahmad
Summary: Melanoma is one of the most common cancers in the US and its incidence is increasing. Immunotherapies have significantly improved survival rates for metastatic melanoma, but half of the patients do not respond to current therapies. Tumor immune evasion is a major factor contributing to this resistance, and new strategies are needed to overcome it.
FRONTIERS IN ONCOLOGY
(2022)
Article
Cell Biology
Rajendra Karki, Balamurugan Sundaram, Bhesh Raj Sharma, SangJoon Lee, R. K. Subbarao Malireddi, Lam Nhat Nguyen, Shelbi Christgen, Min Zheng, Yaqiu Wang, Parimal Samir, Geoffrey Neale, Peter Vogel, Thirumala-Devi Kanneganti
Summary: The study uncovers the role of ADAR1 in suppressing ZBP1-mediated PANoptosis and promoting tumorigenesis. Additionally, the use of IFN-gamma and NEI KPT-330 regresses melanoma in a ZBP1-dependent manner, providing important insights for cancer therapeutic strategies.
Review
Cell Biology
Wei Tang, Jun Chen, Tianlong Ji, Xiufeng Cong
Summary: Melanoma, the deadliest type of skin cancer, can be effectively treated by immune checkpoint blockades (ICBs) such as PD-1/PD-L1 and CTLA-4 inhibitors. However, these inhibitors also have drug resistance and severe immune toxicity. Therefore, developing new immune checkpoint inhibitors like TIGIT is crucial to optimize melanoma therapy. TIGIT, an inhibitory receptor found in T cells, NK cells, and Tregs, plays a role in the occurrence, development, and prognosis of melanoma. This review focuses on the immunosuppressive mechanism of TIGIT and its potential for targeted therapy in melanoma.
CELL DEATH & DISEASE
(2023)
Article
Cardiac & Cardiovascular Systems
Dunpeng Cai, Chenming Sun, Takashi Murashita, Xingyi Que, Shi-You Chen
Summary: This study reveals the crucial role of macrophage activation in abdominal aortic aneurysm (AAA) development. It identifies adenosine deaminase acting on RNA (ADAR1) as a novel mechanism underlying macrophage activation and AAA formation.
CIRCULATION RESEARCH
(2023)
Review
Biology
Valentina Tassinari, Cristina Cerboni, Alessandra Soriani
Summary: ADAR1 mediates immune response modulation by A-to-I editing, preventing the development of autoimmune diseases and cancer. The activity of ADAR1 prevents the recognition of endogenous dsRNA by cellular sensors, avoiding excessive inflammation and IFN-I production.
Article
Multidisciplinary Sciences
Andrew Patterson, Noam Auslander
Summary: This study identifies key mutated processes associated with immune checkpoint inhibitor response in melanoma patients, demonstrating improved predictive capability compared to tumor mutational burden.
NATURE COMMUNICATIONS
(2022)
Review
Oncology
Andrey Rubanov, Pietro Berico, Eva Hernando
Summary: Melanoma is an aggressive skin cancer that relies on early detection for successful treatment. Genetic drivers of melanoma have been identified and targeted therapies have significantly improved patient outcomes. However, resistance to therapy, caused by both genetic alterations and epigenetic reprogramming, remains a challenge.
Review
Oncology
Riyaben P. Patel, Pretashini M. Somasundram, Lorey K. Smith, Karen E. Sheppard, Grant A. McArthur
Summary: By studying the response of melanoma to targeted therapies and immune checkpoint inhibitors, we have identified three phases: early response, minimal residual disease, and disease progression. We explore the effects of these treatments on melanoma cells and the tumor immune microenvironment, with a focus on the role of minimal residual disease in the development of acquired resistance. By uncovering the biology of each therapeutic phase, we can provide a new framework for melanoma treatment, including optimal sequencing strategies and targeting minimal residual disease, to improve clinical outcomes for patients.
CLINICAL AND TRANSLATIONAL MEDICINE
(2023)
Article
Multidisciplinary Sciences
Rowan Howell, James Davies, Matthew A. Clarke, Anna Appios, Yashoda Jayal, Ben Ringham-Terry, Isabel Boned Del Rio, Jasmin Fisher, Clare L. Bennett
Summary: Researchers have developed an in silico model to investigate the interaction between melanomas and Langerhans cells (LCs). The model suggests that melanomas do not activate LC migration to lymph nodes until they reach a critical size, due to a positive TNF-alpha feedback loop. Experimental testing confirms that treating primary tumors with MAPK pathway inhibitors can prevent LC migration. The study also predicts treatment combinations that can bypass LC dysfunction.
Review
Immunology
Valentin Benboubker, Felix Boivin, Stephane Dalle, Julie Caramel
Summary: Immunotherapies targeting negative immune checkpoints have been approved for treating various cancers, but resistance remains a major issue, especially in metastatic melanoma. Non-genetic alterations in cancer cells contribute to therapy resistance and immune evasion. Understanding the phenotypic reprogramming of melanoma cells can lead to new therapeutic strategies for improving outcomes in this aggressive cancer.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Emily J. Lelliott, Stefano Mangiola, Kelly M. Ramsbottom, Magnus Zethoven, Lydia Lim, Peter K. H. Lau, Amanda J. Oliver, Luciano G. Martelotto, Laura Kirby, Claire Martin, Riyaben P. Patel, Alison Slater, Carleen Cullinane, Anthony T. Papenfuss, Nicole M. Haynes, Grant A. McArthur, Jane Oliaro, Karen E. Sheppard
Summary: Combined inhibition of BRAF, MEK, and CDK4/6 in melanoma patients with BRAF(V600) mutation shows potent tumor control effects but may lead to resistance to immune checkpoint blockade.
CANCER IMMUNOLOGY RESEARCH
(2021)
Article
Chemistry, Analytical
Junrong Li, Alain Wuethrich, Zhen Zhang, Jing Wang, Lynlee L. Lin, Andreas Behren, Yuling Wang, Matt Trau
Summary: This study developed a surface-enhanced Raman scattering (SERS) assay to predict the response of melanoma patients to immune checkpoint blockade (ICB) therapy. By measuring both ensemble and single-cell CTCs, the assay revealed tumor heterogeneity and provided a comprehensive CTC phenotype for decision-making.
ANALYTICAL CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Mehrdad Hashemi, Motahare Sadat Ayat Mirdamadi, Yasmin Talebi, Nasrin Khaniabad, Gooya Banaei, Pouria Daneii, Sadaf Gholami, Amin Ghorbani, Alireza Tavakolpournegari, Zoheir Mohammadian Farsani, Ali Zarrabi, Noushin Nabavi, Mohammad Arad Zandieh, Mohsen Rashidi, Afshin Taheriazam, Maliheh Entezari, Haroon Khan
Summary: The field of non-coding RNA has made significant progress in cancer research, and miR-21 plays a crucial role in tumor progression, metabolism reprogramming, metastasis, and drug resistance.
PHARMACOLOGICAL RESEARCH
(2023)
Article
Medicine, Research & Experimental
Ivetta Danylesko, Guy Chowers, Roni Shouval, Michal J. Besser, Elad Jacoby, Avichai Shimoni, Arnon Nagler, Abraham Avigdor
CURRENT RESEARCH IN TRANSLATIONAL MEDICINE
(2020)
Article
Biochemistry & Molecular Biology
Michal J. Besser, Orit Itzhaki, Guy Ben-Betzalel, Douglas B. Zippel, Dragoslav Zikich, Adva Kubi, Karin Brezinger, Abraham Nissani, Michal Levi, Li-at Zeltzer, Alon Ben-Nun, Nethanel Asher, Avichai Shimoni, Arnon Nagler, Gal Markel, Ronnie Shapira-Frommer, Jacob Schachter
MOLECULAR CARCINOGENESIS
(2020)
Article
Hematology
Daphna Hutt, Bella Bielorai, Bella Baturov, Inna Z'orbinski, Natalia Ilin, Etai Adam, Orit Itzhaki, Michal J. Besser, Amos Toren, Elad Jacoby
TRANSFUSION AND APHERESIS SCIENCE
(2020)
Article
Oncology
Orit Itzhaki, Elad Jacoby, Abraham Nissani, Michal Levi, Arnon Nagler, Adva Kubi, Karin Brezinger, Hadar Brayer, Li-at Zeltzer, Meir Rozenbaum, Helly Vernitsky, Gal Markel, Amos Toren, Abraham Avigdor, Jacob Schachter, Michal J. Besser
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2020)
Article
Immunology
Meir Rozenbaum, Amilia Meir, Yarden Aharony, Orit Itzhaki, Jacob Schachter, Ilan Bank, Elad Jacoby, Michal J. Besser
FRONTIERS IN IMMUNOLOGY
(2020)
Article
Biophysics
Ivetta Danylesko, Roni Shouval, Noga Shem-Tov, Ronit Yerushalmi, Elad Jacoby, Michal J. Besser, Avichai Shimoni, Tima Davidson, Katia Beider, Dror Mevorach, Shalev Fried, Arnon Nagler, Abraham Avigdor
Summary: After treatment with anti-CD19 CAR T cells, some patients showed pseudo-progression which could be attributed to immune activation of CAR T cells. Further studies are needed to describe and evaluate the impact of this phenomenon.
BONE MARROW TRANSPLANTATION
(2021)
Article
Oncology
Gilli Galore-Haskel, Eyal Greenberg, Inbal Yahav, Ettai Markovits, Rona Ortenberg, Ronnie Shapira-Fromer, Orit Itzhaki, Jacob Schachter, Michal J. Besser, Gal Markel
Summary: The study showed that a data-driven predictive model based on the levels of miR-34a-5p and miR-22-3p can predict response to TIL-ACT therapy. These two microRNAs may serve as potential biomarkers for TIL-ACT therapy.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2021)
Article
Immunology
Hadas Weinstein-Marom, Gideon Gross, Michal Levi, Hadar Brayer, Jacob Schachter, Orit Itzhaki, Michal J. Besser
Summary: Adoptive T cell therapy (ACT) utilizing genetically modified T cells shows promise for cancer treatment. Optimized protocols for gene delivery into clinical TIL preparations are crucial for enhancing TIL survival and functionality in vivo. This retroviral transduction protocol offers an efficient and reproducible method for genetic modification of TIL.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Shelly Kalaora, Adi Nagler, Deborah Nejman, Michal Alon, Chaya Barbolin, Eilon Barnea, Steven L. C. Ketelaars, Kuoyuan Cheng, Kevin Vervier, Noam Shental, Yuval Bussi, Ron Rotkopf, Ronen Levy, Gil Benedek, Sophie Trabish, Tali Dadosh, Smadar Levin-Zaidman, Leore T. Geller, Kun Wang, Polina Greenberg, Gal Yagel, Aviyah Peri, Garold Fuks, Neerupma Bhardwaj, Alexandre Reuben, Leandro Hermida, Sarah B. Johnson, Jessica R. Galloway-Pena, William C. Shropshire, Chantale Bernatchez, Cara Haymaker, Reetakshi Arora, Lior Roitman, Raya Eilam, Adina Weinberger, Maya Lotan-Pompan, Michal Lotem, Arie Admon, Yishai Levin, Trevor D. Lawley, David J. Adams, Mitchell P. Levesque, Michal J. Besser, Jacob Schachter, Ofra Golani, Eran Segal, Naama Geva-Zatorsky, Eytan Ruppin, Pia Kvistborg, Scott N. Peterson, Jennifer A. Wargo, Ravid Straussman, Yardena Samuels
Summary: The study found that peptides derived from intracellular bacteria can be presented by tumor cells, eliciting an immune response and shedding light on how bacteria influence immune activation and therapy responses.
Article
Oncology
Abraham Nissani, Shaked Lev-Ari, Tomer Meirson, Elad Jacoby, Nethanel Asher, Guy Ben-Betzalel, Orit Itzhaki, Ronnie Shapira-Frommer, Jacob Schachter, Gal Markel, Michal J. Besser
Summary: Different non-myeloablative (NMA) regimens using cyclophosphamide or total body irradiation (TBI) combined with fludarabine have varying impacts on bone marrow suppression and recovery, with the 60Cy/125Flu preconditioning appearing to achieve maximum effect with minimum toxicity.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Oncology
Roni Shouval, Ana Alarcon Tomas, Joshua A. Fein, Jessica R. Flynn, Ettai Markovits, Shimrit Mayer, Aishat Olaide Afuye, Anna Alperovich, Theodora Anagnostou, Michal J. Besser, Connie Lee Batlevi, Parastoo B. Dahi, Sean M. Devlin, Warren B. Fingrut, Sergio A. Giralt, Richard J. Lin, Gal Markel, Gilles Salles, Craig S. Sauter, Michael Scordo, Gunjan L. Shah, Nishi Shah, Ruth Scherz-Shouval, Marcel van den Brink, Miguel-Angel Perales, Maria Lia Palomba
Summary: TP53 mutations/CNAs are important determinants of response and survival in LBCL patients treated with CD19-CAR-T therapy. TP53 alterations are associated with poor treatment outcomes and lower survival rates.
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Oncology
Carlos A. Garcia-Prieto, Lorea Villanueva, Alberto Bueno-Costa, Veronica Davalos, Europa Azucena Gonzalez-Navarro, Manel Juan, Alvaro Urbano-Ispizua, Julio Delgado, Valentin Ortiz-Maldonado, Francesca Del Bufalo, Franco Locatelli, Concetta Quintarelli, Matilde Sinibaldi, Marta Soler, Manuel Castro de Moura, Gerardo Ferrer, Rocio G. Urdinguio, Agustin F. Fernandez, Mario F. Fraga, Diana Bar, Amilia Meir, Orit Itzhaki, Michal J. Besser, Abraham Avigdor, Elad Jacoby, Manel Esteller
Summary: This study revealed that the DNA methylation landscape of patient CART19 cells influences the efficacy of cellular immunotherapy treatment in patients with B-cell malignancies. The establishment of an epigenetic signature, termed EPICART, associated with complete response, was found to be predictive of patient clinical outcomes.
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2022)
Article
Hematology
Elad Jacoby, Bella Bielorai, Daphna Hutt, Orit Itzhaki, Etai Adam, Diana Bar, Michal J. Besser, Amos Toren
Summary: This study reported the long-term outcome of 37 children and young adults treated with autologous CD19 CAR-T cells, with a complete remission rate of 86% and 41% three-year EFS. Prelymphodepletion disease burden and molecular MRD negativity following CAR-T cells are predictors of long-term outcome.
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Article
Cell Biology
Katia Beider, Orit Itzhaki, Jacob Schachter, Ania Hava Grushchenko-Polaq, Valeria Voevoda-Dimenshtein, Evgenia Rosenberg, Olga Ostrovsky, Olivia Devillers, Ronnie Shapira Frommer, Li-At Zeltzer, Amos Toren, Elad Jacoby, Avichai Shimoni, Abraham Avigdor, Arnon Nagler, Michal J. Besser
Summary: This study reveals that CD19 CAR T cells from non-responding patients with B cell malignancies exhibit exhausted/senescent phenotype and functional impairment. The findings provide insights into potential mediators of resistance and pave the way for enhancing the efficacy and durability of CAR T therapy in B cell malignancies.
Article
Hematology
Meirav Kedmi, Roni Shouval, Shalev Fried, David Bomze, Joshua Fein, Zachary Cohen, Ivetta Danilesko, Noga Shem-Tov, Ronit Yerushalmi, Elad Jacoby, Michal Besser, Avichai Shimoni, Arnon Nagler, Abraham Avigdor
Summary: Anti CD19 CAR T-cell therapy has shown good efficacy in relapsed and refractory aggressive B-cell lymphoma. Locally produced autologous CD19-directed CAR T-cell product with a short production time and good progression-free and overall survival is a feasible therapeutic option.
TRANSPLANTATION AND CELLULAR THERAPY
(2022)