Article
Medicine, General & Internal
Brian Mehling, DongCheng Wu, Ellen O'Gorman, Daniel Sheridan, Doreen Santora, Renata Mihalyova
Summary: This study characterized the safety and efficacy of DC-CIK therapy in two patients with previously treated chronic lymphocytic leukemia or peritoneal cancer. Both patients received conventional chemotherapy treatment along with 1-2 treatments of DC-CIK therapy over the course of 1 year. The results showed that DC-CIK therapy had no treatment-related adverse events and led to improved treatment response, increased chemotherapy tolerance, and prolonged survival compared to typical 5-year survival rates.
FRONTIERS IN MEDICINE
(2023)
Article
Oncology
Iria Fernandez Botana, Giulia Pagano, Etienne Moussay, Jerome Paggetti
Summary: Chronic lymphocytic leukemia is the most common adult leukemia in the western world, and its interactions with the surrounding immune landscape are crucial for therapeutic interventions. Recent research has shown that the cytokine IL-27 exerts a strong anti-tumor role in CLL through a T-cell mediated mechanism.
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.
Review
Oncology
Elisavet Vlachonikola, Kostas Stamatopoulos, Anastasia Chatzidimitriou
Summary: The treatment of chronic lymphocytic leukemia (CLL) is continuously evolving, with immunotherapy emerging as a therapeutic option to boost immune responses against tumors. However, not all patients benefit from this approach, partly due to dysfunctional T cells in CLL. The tumor microenvironment (TME) is also crucial in impacting immune responses and tumor growth, highlighting the importance of understanding T cell defects and finding ways to overcome them for effective immunotherapy in CLL.
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.
Review
Oncology
Xavier Roussel, Francine Garnache Ottou, Florian Renosi
Summary: Plasmacytoid dendritic cells (pDC) are the main type I interferon-producing cells in humans and are capable of regulating innate and adaptive immune responses. Tumor infiltration by pDC is well-documented in various cancers and is associated with unfavorable clinical outcomes. While Blastic Plasmacytoid Dendritic Cells Neoplasm (BPDCN) is a well-described aggressive leukemia derived from pDCs, the understanding of tumor infiltration by mature pDCs in Myeloid Neoplasms (MN) is limited. This review aims to provide a comprehensive overview of pDC biology in MN, emphasizing the need for further research into pDC oncogenesis and immune responses for better therapeutic strategies.
Article
Immunology
Seung-Ji Kang, Ki-Jeong Park, Hye-Mi Jin, Young-Nan Cho, Tae Hoon Oh, Seong Eun Kim, Uh Jin Kim, Kyung-Hwa Park, Sook-In Jung, Tae-Ok Kim, Hyo Shin Kim, Young-Goun Jo, Jae Kyun Ju, Seung-Jung Kee, Yong-Wook Park
Summary: This study reveals that circulating pDCs and cDCs are numerically deficient and functionally impaired in scrub typhus patients. Changes in the expression levels of surface phenotypes of pDCs and cDCs may be influenced by pro-inflammatory cytokines.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Oncology
Hongyan Liao, Jiang Yu, Yu Liu, Sha Zhao, Huanling Zhu, Dongsheng Xu, Nenggang Jiang, Qin Zheng
Summary: This case demonstrates for the first time that prominent pDC proliferation can be associated with lymphoid neoplasms and can exhibit blastic morphology and immunophenotype. The underlying mechanism of the coexistence of these two blastic populations remains unknown.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2022)
Article
Oncology
Wei Wang, Jie Xu, Joseph D. Khoury, Naveen Pemmaraju, Hong Fang, Roberto N. Miranda, C. Cameron Yin, Siba El Hussein, Fuli Jia, Zhenya Tang, Shimin Hu, Marina Konopleva, L. Jeffrey Medeiros, Sa A. Wang
Summary: This study investigated the immunophenotypic and molecular profiles of pDC-AML and BPDCN and found that they have different phenotypes and mutation profiles, indicating that they are two distinct entities.
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)
Review
Oncology
Carol Moreno, Cecilia Munoz, Maria Jose Terol, Jose-Angel Hernandez-Rivas, Miguel Villanueva
Summary: Chronic Lymphocytic Leukemia is a hematological malignancy characterized by uncontrolled B-cell proliferation and severe immune dysfunction. Developing therapeutic strategies that target both malignant B-cells and enhance the patient's immune response could be clinically relevant in treating CLL patients.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2021)
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
Multidisciplinary Sciences
Meiling Zheng, Zhi Hu, Xiaole Mei, Lianlian Ouyang, Yang Song, Wenhui Zhou, Yi Kong, Ruifang Wu, Shijia Rao, Hai Long, Wei Shi, Hui Jing, Shuang Lu, Haijing Wu, Sujie Jia, Qianjin Lu, Ming Zhao
Summary: This study compares the differences between cutaneous lesions from DLE and SLE patients and healthy controls using single-cell RNA sequencing data. The findings reveal differential immune cell recruitment, cell type, and gene expression, highlighting potential therapeutic targets for lupus erythematosus.
NATURE COMMUNICATIONS
(2022)
Review
Oncology
Zong-Han Wang, Wei Li, Hao Dong, Fujun Han
Summary: Chronic lymphocytic leukemia (CLL) is a common hematological disease with a high incidence in western countries. Conventional chemotherapy and targeted therapeutic drugs have limitations in high-risk patients. Immunotherapy, particularly using natural killer (NK) cells, has shown potential for improved prognosis. NK cells enhance immune response through various mechanisms, including antibody-dependent cytotoxicity (ADCC), allogeneic NK cell therapy, and CAR-NK cell therapy. This article reviews the characteristics of NK cells, their receptors, and the advantages and disadvantages of NK cell-based immunotherapies for CLL.
FRONTIERS IN ONCOLOGY
(2023)
Review
Oncology
Billy Michael Chelliah Jebaraj, Stephan Stilgenbauer
Summary: Telomeres play a crucial role in chronic lymphocytic leukemia (CLL), with their dysfunction shaping the disease progression. Members of the shelterin complex and TERT activation are closely associated with CLL cell survival and proliferation.
FRONTIERS IN ONCOLOGY
(2021)
Article
Hematology
Ella R. Thompson, Tamia Nguyen, Yamuna Kankanige, John F. Markham, Mary Ann Anderson, Sasanka M. Handunnetti, Rachel Thijssen, Paul Sung-Hao Yeh, Constantine S. Tam, John F. Seymour, Andrew W. Roberts, David A. Westerman, Piers Blombery
Summary: This study revealed the clonal complexity of resistance to Bruton tyrosine kinase inhibitors and B-cell lymphoma 2 inhibitors in chronic lymphocytic leukemia through targeted single-cell DNA sequencing. The findings showed mutual exclusivity between multiple resistance mutations, variable clonal co-occurrence of mutations affecting different targeted agents, and multiple independent emergences of identical nucleotide changes leading to canonical resistance mutations.
Article
Hematology
Constantine S. Tam, John N. Allan, Tanya Siddiqi, Thomas J. Kipps, Ryan Jacobs, Stephen Opat, Paul M. Barr, Alessandra Tedeschi, Livio Trentin, Rajat Bannerji, Sharon Jackson, Bryone J. Kuss, Carol Moreno, Edith Szafer-Glusman, Kristin Russell, Cathy Zhou, Joi Ninomoto, James P. Dean, William G. Wierda, Paolo Ghia
Summary: The CAPTIVATE study is an international phase 2 study that investigated the efficacy of fixed-duration treatment with ibrutinib plus venetoclax in patients with chronic lymphocytic leukemia. The study showed promising results, with high complete response rates and durable responses, even in high-risk patients.
Article
Hematology
Dale Jobson, Christopher J. McCormack, Victoria Mar, Constantine Tam, Michael A. Henderson
Summary: This retrospective case-controlled study examined the impact of CLL on melanoma-specific survival and recurrence. The results showed that CLL was associated with significantly worse melanoma outcomes, and prior CLL treatment did not affect the melanoma outcomes.
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Article
Hematology
Tycel Phillips, Henry Chan, Constantine S. Tam, Alessandra Tedeschi, Patrick Johnston, Sung Yong Oh, Stephen Opat, Hyeon-Seok Eom, Heather Allewelt, Jennifer C. Stern, Ziwen Tan, William Novotny, Jane Huang, Judith Trotman
Summary: The study demonstrates favorable outcomes for patients with relapsed/refractory marginal zone lymphoma and follicular lymphoma treated with the selective Bruton's tyrosine kinase inhibitor zanubrutinib. The results support zanubrutinib as a potentially meaningful addition to available therapies for these patients.
Article
Cell Biology
Pin Shie Quah, Vivien Sutton, Eden Whitlock, William A. Figgett, Daniel M. Andrews, Kirsten A. Fairfax, Fabienne Mackay
Summary: The role of B-cell-activating factor (BAFF) in the homeostasis of natural killer (NK) cells has been studied. BAFF signaling through BAFF receptor is essential for sustaining NK cell numbers in the spleen, but BAFF is dispensable for NK cell maturation. NK cells from BAFF deficient and BAFF transgenic mice showed similar interferon-gamma production and tumor cell killing capacity compared to wild-type mice. NK cells do not express BAFF receptors in the steady state or in a SLE mouse model.
IMMUNOLOGY AND CELL BIOLOGY
(2022)
Article
Oncology
Peter Hillmen, Barbara Eichhorst, Jennifer R. Brown, Nicole Lamanna, Susan M. O'Brien, Constantine S. Tam, Lugui Qiu, Maciej Kazmierczak, Keshu Zhou, Martin Simkovic, Jiri Mayer, Amanda Gillespie-Twardy, Mazyar Shadman, Alessandra Ferrajoli, Peter S. Ganly, Robert Weinkove, Sebastian Grosicki, Andrzej Mital, Tadeusz Robak, Anders Osterborg, Habte A. Yimer, Tommi Salmi, Meng Ji, Jessica Yecies, Adam Idoine, Kenneth Wu, Jane Huang, Wojciech Jurczak
Summary: The study compared the efficacy and safety of zanubrutinib and ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia. The results showed that zanubrutinib had better outcomes in terms of efficacy, atrial fibrillation rate, and cardiac safety compared to ibrutinib.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Oncology
John N. Allan, Ian W. Flinn, Tanya Siddiqi, Paolo Ghia, Constantine S. Tam, Thomas J. Kipps, Paul M. Barr, Anna Elinder Camburn, Alessandra Tedeschi, Xavier C. Badoux, Ryan Jacobs, Bryone J. Kuss, Livio Trentin, Cathy Zhou, Anita Szoke, Christopher Abbazio, William G. Wierda
Summary: The CAPTIVATE study demonstrates that fixed-duration ibrutinib plus venetoclax is effective in controlling chronic lymphocytic leukemia, including patients with high-risk genomic features. This treatment provides durable progression-free survival and similar overall survival rates.
CLINICAL CANCER RESEARCH
(2023)
Article
Clinical Neurology
Sudha Raghunath, Yifat Glikmann-Johnston, Fabien B. Vincent, Eric F. Morand, Julie C. Stout, Alberta Hoi
Summary: This study aims to characterize the prevalence and patterns of cognitive dysfunction in SLE. The results showed that SLE patients performed significantly worse than healthy controls on every cognitive test, with verbal fluency, working memory, and attention being the most affected domains. The study supports the use of a binary definition of cognitive dysfunction in SLE.
JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY
(2023)
Article
Hematology
C. S. Tam, P. Kapoor, J. J. Castillo, C. Buske, S. M. Ansell, A. R. Branagan, E. Kimby, Y. Li, M. L. Palomba, L. Qiu, M. Shadman, J. P. Abeykoon, S. Sarosiek, J. M. Vos, S. Yi, D. Stephens, D. Roos-Weil, A. M. Roccaro, P. Morel, N. C. Munshi, K. C. Anderson, J. San-Miguel, R. Garcia-Sanz, M. A. Dimopoulos, S. P. Treon, M. J. Kersten
Summary: Recent advances in understanding WM biology have influenced the development of novel agents and improved knowledge of WM genomics. CP7 examined completed and ongoing clinical trials and made recommendations for future trials, prioritizing limited duration and novel agent combinations. Evaluating MYD88, CXCR4, and TP53 at baseline and using bendamustine-rituximab or dexamethasone, rituximab and cyclophosphamide as standard treatments were suggested. Unanswered questions include defining frailty, determining the importance of achieving VGPR within a specific time frame, and providing optimal treatment for WM populations with special needs.
SEMINARS IN HEMATOLOGY
(2023)
Letter
Hematology
Matko Kalac, Salvia Jain, Constantine S. Tam, Zhengrui Xiao, Francesca Montanari, Jennifer Kanakry, Bryan D. Huber, Mendel Goldfinger, Owen A. O'Connor, Enrica Marchi
Letter
Hematology
Constantine S. Tam, Judith Trotman, Stephen Opat, Jennifer C. Stern, Heather Allewelt, Kunthel By, William Novotny, Jane Huang, Alessandra Tedeschi
Article
Hematology
Carol Moreno, Isabelle G. Solman, Constantine S. Tam, Andrew Grigg, Lydia Scarfo, Thomas J. Kipps, Srimathi Srinivasan, Raghuveer Singh Mali, Cathy Zhou, James P. Dean, Edith Szafer-Glusman, Michael Choi
Summary: This study evaluated immune cell subsets in patients with CLL who received different treatments. The results demonstrated successful elimination of CLL cells and restoration of normal immune cells in some patients.
Review
Cardiac & Cardiovascular Systems
Ahmed M. Al-Kaisey, William Figgett, Joshua Hawson, Fabienne Mackay, Stephen A. Joseph, Jonathan M. Kalman
Summary: In the past decade, there has been growing interest in understanding the role of gut microbiota in the development of atrial fibrillation (AF). Studies have linked gut dysbiosis to traditional risk factors for AF such as hypertension and obesity, but whether gut dysbiosis directly affects arrhythmogenesis in AF remains unclear. This article provides an overview of the current understanding of the impact of gut dysbiosis and associated metabolites on AF, as well as discusses current therapeutic strategies and future directions.
ARRHYTHMIA & ELECTROPHYSIOLOGY REVIEW
(2023)
Article
Oncology
Thomas E. Lew, Edward R. Scheffer Cliff, Michael Dickinson, Constantine S. Tam, John F. Seymour, Piers Blombery, Ashish Bajel, David Ritchie, Amit Khot
Summary: Cytarabine-containing chemoimmunotherapy followed by autologous transplantation and rituximab maintenance achieves durable remissions for most patients with mantle cell lymphoma (MCL). However, patients with TP53-mutated disease have poor outcomes with standard approaches. Allogeneic stem cell transplantation (alloSCT) can be curative in MCL, including patients with TP53-mutated disease, and should be considered as an earlier treatment option for this subgroup.
LEUKEMIA & LYMPHOMA
(2023)
Review
Oncology
Constantine S. Tam, Javier L. Munoz, John F. Seymour, Stephen Opat
Summary: This article reviews the development of zanubrutinib, a next-generation BTK inhibitor, and its clinical applications in the treatment of B-cell malignancies. Zanubrutinib has shown greater specificity and improved pharmacokinetic properties compared to the first-generation inhibitor, ibrutinib, resulting in improved activity and safety outcomes. The clinical program of zanubrutinib has expanded significantly, with ongoing studies in various hematological malignancies and in combination with other therapies.
BLOOD CANCER JOURNAL
(2023)