Article
Hematology
Emma Kennedy, Eve Coulter, Emma Halliwell, Nuria Profitos-Peleja, Elisabeth Walsby, Barnaby Clark, Elizabeth H. Phillips, Thomas A. Burley, Simon Mitchell, Stephen Devereux, Christopher D. Fegan, Christopher Jones, Rosalynd Johnston, Tim Chevassut, Ralph Schulz, Martina Seiffert, Angelo Agathanggelou, Ceri Oldreive, Nicholas Davies, Tatjana Stankovic, Triantafillos Liloglou, Chris Pepper, Andrea G. S. Pepper
Summary: Despite the advancements in B-cell receptor-targeted inhibitors, CLL remains incurable. TLR9 activation by unmethylated DNA is associated with disease progression in CLL. High TLR9 expression promotes CLL cell migration and disease progression, while dual targeting of TLR9 and BTK shows strong synergism as a potential treatment strategy for this incurable disease.
Article
Medicine, General & Internal
Barbara Eichhorst, Carsten U. Niemann, Arnon P. Kater, Moritz Fuerstenau, Julia von Tresckow, Can Zhang, Sandra Robrecht, Michael Gregor, Gunnar Juliusson, Patrick Thornton, Philipp B. Staber, Tamar Tadmor, Vesa Lindstrom, Caspar da Cunha-Bang, Christof Schneider, Christian B. Poulsen, Thomas Illmer, Bjoern Schoettker, Thomas Noesslinger, Ann Janssens, Ilse Christiansen, Michael Baumann, Henrik Frederiksen, Marjolein van der Klift, Ulrich Jaeger, Maria B. L. Leys, Mels Hoogendoorn, Kourosh Lotfi, Holger Hebart, Tobias Gaska, Harry Koene, Lisbeth Enggaard, Jereon Goede, Josien C. Regelink, Anouk Widmer, Florian Simon, Nisha De Silva, Anna-Maria Fink, Jasmin Bahlo, Kirsten Fischer, Clemens-Martin Wendtner, Karl A. Kreuzer, Matthias Ritgen, Monika Brueggemann, Eugen Tausch, Mark-David Levin, Marinus van Oers, Christian Geisler, Stephan Stilgenbauer, Michael Hallek
Summary: In fit patients with CLL, venetoclax-obinutuzumab, with or without ibrutinib, showed superior results compared to chemoimmunotherapy as a first-line treatment, with higher rates of undetectable minimal residual disease and progression-free survival.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Article
Oncology
Andrea N. Mazzarello, Mark Fitch, Martina Cardillo, Anita Ng, Sabreen Bhuiya, Esha Sharma, Davide Bagnara, Jonathan E. Kolitz, Jacqueline C. Barrientos, Steven L. Allen, Kanti R. Rai, Joanna Rhodes, Marc K. Hellerstein, Nicholas Chiorazzi
Summary: Chronic lymphocytic leukemia (CLL) clones contain subpopulations with different ages and phenotypes. The youngest cells are recently born and proliferative, while the oldest cells are resting. Cells with high levels of surface membrane proteins are younger, and stimulation through these proteins results in a phenotype consistent with in vivo observations. Older cells are less sensitive to drug inhibition.
Article
Audiology & Speech-Language Pathology
Chao-Hui Yang, Chung-Feng Hwang, Jiin-Haur Chuang, Wei-Shiung Lian, Feng-Sheng Wang, Ming-Yu Yang
Summary: The TLR signaling pathway plays a key role in the innate immune response to systemic infection. While systemic TLR7 agonist did not significantly affect ototoxicity, TLR9 agonist exacerbated kanamycin-induced ototoxicity and inflammation in the cochlea. This study suggests that patients with viral infections may experience more severe hearing loss when treated with aminoglycosides.
Article
Neurosciences
Yu Chen, Hui Chen, Xiao-Chen Li, Wen-Li Mi, Yu-Xia Chu, Yan-Qing Wang, Qi-Liang Mao-Ying
Summary: Toll like receptor 9 (TLR9) is a critical sensor involved in danger-associated molecular patterns (DAMPs), and its role in inflammatory pain is not well understood. This study demonstrates that downregulation of neuronal TLR9 in the spinal cord can prevent CFA-induced persistent hypersensitivity, suggesting it may be a potential treatment target for inflammatory pain.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Review
Biochemistry & Molecular Biology
Veronika Mancikova, Michal Smida
Summary: CAR T-cell therapy has shown remarkable remissions in difficult-to-treat patients with B-cell malignancies, but the efficacy in chronic lymphocytic leukemia patients is the lowest among B-cell tumors, requiring further investigation into treatment mechanisms and failure reasons.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Hematology
Freda K. Stevenson, Francesco Forconi, Thomas J. Kipps
Summary: Research into chronic lymphocytic leukemia has led to significant improvements in the assessment and treatment of patients, with designer drugs now successfully targeting tumor cells based on their biology. Classifying CLL into unmutated (U) and mutated (M) diseases based on the mutational status of IGHV sequences reveals distinct origins, biology, and clinical behaviors for each. Despite advances, challenges such as cell-escape strategies and immunosuppression remain, necessitating continued research into CLL biology.
Article
Cardiac & Cardiovascular Systems
Tomohito Ishikawa, Kohtaro Abe, Mariko Takana-Ishikawa, Keimei Yoshida, Takanori Watanabe, Satomi Imakiire, Kazuya Hosokawa, Mayumi Hirano, Katsuya Hirano, Hiroyuki Tsutsui
Summary: This study found that TLR9 is involved in the development of pulmonary hypertension via activation of the NF-kappa B-IL-6 pathway. Inhibition of TLR9 may be a novel therapeutic strategy for pulmonary hypertension.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2021)
Review
Oncology
Laura Patrussi, Nagaja Capitani, Cosima T. Baldari
Summary: IL-9, a soluble factor secreted by immune cells, has been found in several tumor niches, with dual roles in promoting or counteracting tumor development depending on the specific type of cancer. Recent studies implicate IL-9 in chronic lymphocytic leukemia pathogenesis, yet the molecular mechanisms remain unclear.
Article
Oncology
Fuli Fan, Hyeon Joo Yoo, Sophia Stock, Lei Wang, Yibin Liu, Maria-Luisa Schubert, Sanmei Wang, Brigitte Neuber, Angela Hueckelhoven-Krauss, Ulrike Gern, Anita Schmitt, Carsten Mueller-Tidow, Peter Dreger, Michael Schmitt, Leopold Sellner
Summary: The use of ibrutinib has been shown to improve the viability and expansion of CART cells derived from CLL patients, enriching them with less-differentiated naive-like T cell subsets and reducing exhaustion marker expression. Additionally, ibrutinib enhances the cytokine release capacity of CLL patient-derived CART cells, suggesting it can improve the yield and function of these cell products.
INTERNATIONAL JOURNAL OF CANCER
(2021)
Article
Immunology
Huanghui Wu, Han Bao, Cong Liu, Qiao Zhang, Ailing Huang, Minxue Quan, Chunhui Li, Ying Xiong, Guozhong Chen, Lichao Hou
Summary: This study investigated the role and mechanism of extracellular nucleosomes and histones, as damage-associated molecular patterns (DAMPs), in progressive neuroinflammation and chronic stress-related emotional disorders. It found that extracellular nucleosomes accelerate microglial inflammation via Clec2d and TLR9, contributing to chronic stress-induced emotional disorders.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Damian Kovalovsky, Jeong Heon Yoon, Matthew G. Cyr, Samantha Simon, Elisaveta Voynova, Christoph Rader, Adrian Wiestner, Julie Alejo, Stefania Pittaluga, Ronald E. Gress
Summary: A novel CAR-T cell therapy targeting Siglec-6 for chronic lymphocytic leukemia was developed and shown to specifically target CLL cells. Additionally, Siglec-6 was identified as a potential target for immunotherapy based on the findings of this study.
Review
Immunology
Mengyuan Kou, Liying Wang
Summary: This review focuses on Toll-like receptor 9 (TLR9), an important intracellular pattern recognition receptor in the immune system. TLR9 can recognize CpG DNA in endosomes, but it can also be expressed on the membrane surface of certain immune and non-immune cells, where it plays an immunomodulatory role. This review provides a theoretical reference for the application of TLR9 modulators.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Kristan V. Piroeva, Charlotte Mcdonald, Charalampos Xanthopoulos, Chelsea Fox, Christopher T. Clarkson, Jan-Philipp Mallm, Yevhen Vainshtein, Luminita Ruje, Lara C. Klett, Stephan Stilgenbauer, Daniel Mertens, Efterpi Kostareli, Karsten Rippe, Vladimir B. Teif
Summary: This study compared the nucleosome positions in chronic lymphocytic leukemia (CLL) patients and healthy individuals, and found significant changes in nucleosome positioning in CLL. The spacing between nucleosomes was shortened, and changes in nucleosome occupancy were linked to chromatin remodeling and reduced DNA methylation. Nucleosome positioning can be used to classify CLL subtypes and monitor disease progression.
Article
Biochemistry & Molecular Biology
Nannan Pang, Xierenguli Alimu, Rong Chen, Maliya Muhashi, Jiajia Ma, Gang Chen, Fang Zhao, Lei Wang, Jianhua Qu, Jianbing Ding
Summary: This study revealed that Tim-3 was overexpressed in CLL patients, along with elevated levels of Galectin-9/Tim-3 signaling pathway, which were associated with disease progression. By negatively regulating CD4(+) T cells, the activated Galectin-9/Tim-3 pathway suppressed Th1 effector function and promoted Treg cells to participate in immune escape of CLL. These findings suggest that this pathway could be a potential target for immunotherapy in CLL patients.
Article
Hematology
Eleonora Fonte, Andreas Agathangelidis, Daniele Reverberi, Stavroula Ntoufa, Lydia Scarfo, Pamela Ranghetti, Giovanna Cutrona, Alessandra Tedeschi, Aliki Xochelli, Federico Caligaris-Cappio, Maurilio Ponzoni, Chrysoula Belessi, Zadie Davis, Miguel A. Piris, David Oscier, Paolo Ghia, Kostas Stamatopoulos, Marta Muzio
Article
Immunology
Stavroula Ntoufa, Nikos Papakonstantinou, Benedetta Apollonio, Maria Gounari, Chrysi Galigalidou, Eleonora Fonte, Achilles Anagnostopoulos, Chrysoula Belessi, Marta Muzio, Paolo Ghia, Kostas Stamatopoulos
JOURNAL OF IMMUNOLOGY
(2016)
Review
Oncology
Stavroula Ntoufa, Maria Giovanna Villa, Kostas Stamatopoulos, Paolo Ghia, Marta Muzio
SEMINARS IN CANCER BIOLOGY
(2016)
Article
Hematology
Eleonora Fonte, Maria Giovanna Vilia, Daniele Reverberi, Ilenia Sana, Lydia Scarfo, Pamela Ranghetti, Ugo Orfanelli, Simone Cenci, Giovanna Cutrona, Paolo Ghia, Marta Muzio
Article
Oncology
Maria Giovanna Vilia, Eleonora Fonte, Tania Veliz Rodriguez, Marta Tocchetti, Pamela Ranghetti, Lydia Scarfo, Nikos Papakonstantinou, Stavroula Ntoufa, Kostas Stamatopoulos, Paolo Ghia, Marta Muzio
LEUKEMIA & LYMPHOMA
(2017)
Article
Hematology
Eleonora Fonte, Maria Giovanna Vilia, Daniele Reverberi, Ilenia Sana, Lydia Scarfo, Pamela Ranghetti, Ugo Orfanelli, Simone Cenci, Giovanna Cutrona, Paolo Ghia, Marta Muzio
Letter
Oncology
Maria Gounari, Stavroula Ntoufa, Marina Gerousi, Maria Giovanna Vilia, Theodoros Moysiadis, Konstantia Kotta, Nikos Papakonstantinou, Lydia Scarfo, Andreas Agathangelidis, Eleonora Fonte, Pamela Ranghetti, Athanasia Nenou, Aliki Xochelli, Marta Coscia, Alessandra Tedeschi, Niki Stavroyianni, Marta Muzio, Kostas Stamatopoulos, Paolo Ghia
Article
Oncology
Federica Riva, Maurilio Ponzoni, Domenico Supino, Maria Teresa Sabrina Bertilaccio, Nadia Polentarutti, Matteo Massara, Fabio Pasqualini, Roberta Carriero, Anna Innocenzi, Achille Anselmo, Tania Veliz-Rodriguez, Giorgia Simonetti, Hans-Joachim Anders, Federico Caligaris-Cappio, Alberto Mantovani, Marta Muzio, Cecilia Garlanda
CANCER IMMUNOLOGY RESEARCH
(2019)
Article
Hematology
Vincenza Simona Delvecchio, Ilenia Sana, Maria Elena Mantione, Maria Giovanna Vilia, Pamela Ranghetti, Alessandra Rovida, Piera Angelillo, Lydia Scarfo, Paolo Ghia, Marta Muzio
BRITISH JOURNAL OF HAEMATOLOGY
(2020)
Review
Oncology
Ilenia Sana, Maria Elena Mantione, Piera Angelillo, Marta Muzio
Summary: In recent years, significant progress has been made in the clinical management of chronic lymphocytic leukemia and other B-cell malignancies by targeting B-cell receptor signaling molecules. However, a proportion of patients remain uncured, leading to efforts in studying new potential targets. NFAT is overexpressed and constitutively activated in CLL, with targeting this molecule impacting on CLL cell viability.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Maria Elena Mantione, Ilenia Sana, Maria Giovanna Vilia, Michela Riba, Claudio Doglioni, Alessandro Larcher, Umberto Capitanio, Marta Muzio
Summary: Renal cell carcinoma shows a specific pattern of inflammatory receptor expression, with a downregulation of SIGIRR. IL1 stimulation activates the inflammatory pathway in ccRCC cells and induces the expression of various pro-tumor genes. Manipulating this pathway may be beneficial for ccRCC treatment.
FRONTIERS IN ONCOLOGY
(2022)
Meeting Abstract
Hematology
Marina Gerousi, Anastasia Iatrou, Antonios Mingos, Nikolaos Pechlivanis, Stavroula Ntoufa, Maria Gounari, Nikos Papakonstantinou, Georgios Karakatsoulis, Eleni Kotroni, Ioannis Sarrigeorgiou, Zadie Davis, Peggy Lymberi, David Oscier, Ioanna Sakellari, Alexandra Traverse-Glehen, Niki Stavroyianni, Fotis Psomopoulos, Marta Muzio, Paolo Ghia, Anastasia Chatzidimitriou, Kostas Stamatopoulos
Meeting Abstract
Oncology
Ilenia Sana, Maria Elena Mantione, Simona Vincenza Delvecchio, Ettore Zapparoli, Michela Riba, Pamela Ranghetti, Piera Angelillo, Lydia Scarfo, Paolo Ghia, Marta Muzio
LEUKEMIA & LYMPHOMA
(2020)
Article
Biochemistry & Molecular Biology
Maria Giovanna Vilia, Marta Tocchetti, Eleonora Fonte, Ilenia Sana, Marta Muzio
EUROPEAN CYTOKINE NETWORK
(2017)