Review
Immunology
Yanyan Liu, Yongping Song, Qingsong Yin
Summary: This review summarizes the effects of ibrutinib on the tumor microenvironment and cellular immunity in patients with CLL, particularly focusing on the behavior and function of T cells. The potential mechanisms of ibrutinib are explored, providing a basis for the clinical benefits of long-term ibrutinib treatment and combined therapy based on T-cell-based immunotherapies.
FRONTIERS IN IMMUNOLOGY
(2022)
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.
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
Oncology
Maria Cristina Puzzolo, Ilaria Del Giudice, Nadia Peragine, Paola Mariglia, Maria Stefania De Propris, Luca Vincenzo Cappelli, Livio Trentin, Gianluigi Reda, Antonio Cuneo, Stefano Molica, Alfonso Piciocchi, Valentina Arena, Francesca Romana Mauro, Anna Guarini, Robin Foa
Summary: Research suggests that ibrutinib treatment can reverse T-cell polarization in chronic lymphocytic leukemia (CLL), decreasing Th2 cells and increasing Th1 cells, with a gradual reduction in the Th2/Th1 ratio after treatment initiation. Furthermore, patients with a Th2/Th1 ratio below 0.088 at M8 are more likely to achieve complete remission (CR).
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Elisavet Vlachonikola, Nikolaos Pechlivanis, Georgios Karakatsoulis, Electra Sofou, Glykeria Gkoliou, Sabine Jeromin, Niki Stavroyianni, Pamela Ranghetti, Lydia Scarfo, Cecilia Osterholm, Larry Mansouri, Sofia Notopoulou, Alexandra Siorenta, Achilles Anagnostopoulos, Paolo Ghia, Claudia Haferlach, Richard Rosenquist, Fotis Psomopoulos, Anastasia Kouvatsi, Panagiotis Baliakas, Kostas Stamatopoulos, Anastasia Chatzidimitriou
Summary: Microenvironmental interactions between the malignant clone and T cells are crucial in the development of CLL. The study identifies distinct T cell receptor profiles in patients with different genomic aberrations, suggesting different selection processes. Abnormal protein expression and gene dosage effects from recurrent genomic aberrations may provide CLL-specific antigens for T cells.
FRONTIERS IN ONCOLOGY
(2023)
Article
Oncology
Najmeh Bozorgmehr, Mark Hnatiuk, Anthea C. Peters, Shokrollah Elahi
Summary: This study found that CD26(+)CD8(+) T cells are reduced in chronic lymphocytic leukemia (CLL), but they possess polyfunctionality and durability, making them potential candidates for immunotherapy. Additionally, malignant B cells induce apoptosis of CD26(+)CD8(+) T cells through the release of Galectin-9.
EXPERIMENTAL HEMATOLOGY & ONCOLOGY
(2023)
Article
Oncology
Maria Joao Baptista, Sivasubramanian Baskar, Erika M. Gaglione, Keyvan Keyvanfar, Inhye E. Ahn, Adrian Wiestner, Clare Sun
Summary: In CLL patients, Ibrutinib treatment increases clonality of the TCR repertoire, with stable TCR clonality in patients with sustained remission and decreased TCR clonality in patients with disease progression. Additionally, T cells from responding patients show cytotoxicity against autologous CLL cells in vitro.
CLINICAL CANCER RESEARCH
(2021)
Article
Hematology
Adam S. Kittai, Ying Huang, Kyle A. Beckwith, Seema A. Bhat, David A. Bond, John C. Byrd, Daniel Goldstein, Michael R. Grever, Cecelia Miller, Kerry A. Rogers, Max Yano, Jennifer A. Woyach
Summary: This retrospective analysis found that progression on treatment, higher LDH levels, and lymphadenopathy without lymphocytosis were independent prognostic factors for the development of Richter's Transformation in CLL patients treated with ibrutinib. Additionally, the prognosis for Richter's Transformation remained poor.
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
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
Oncology
John C. Byrd, Peter Hillmen, Paolo Ghia, Arnon P. Kater, Asher Chanan-Khan, Richard R. Furman, Susan O'Brien, Mustafa Nuri Yenerel, Arpad Illes, Neil Kay, Jose A. Garcia-Marco, Anthony Mato, Javier Pinilla-Ibarz, John F. Seymour, Stephane Lepretre, Stephan Stilgenbauer, Tadeusz Robak, Wayne Rothbaum, Raquel Izumi, Ahmed Hamdy, Priti Patel, Kara Higgins, Sophia Sohoni, Wojciech Jurczak
Summary: In this study, acalabrutinib was found to be noninferior to ibrutinib in terms of progression-free survival in patients with CLL, with a lower incidence of cardiovascular adverse events. This suggests that acalabrutinib may be a more tolerable option for continuous therapy in this patient population.
JOURNAL OF CLINICAL ONCOLOGY
(2021)
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
Pharmacology & Pharmacy
Fanny Gallais, Loic Ysebaert, Fabien Despas, Sandra De Barros, Lucie Oberic, Ben Allal, Etienne Chatelut, Melanie White-Koning
Summary: This study developed the first PK-PD model for ALC in patients with CLL under ibrutinib treatment. The results of the model suggested that estimated lymphocyte counts in tissues and blood could be used as an early predictor of treatment response in CLL patients.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2021)
Review
Medicine, General & Internal
Mazyar Shadman
Summary: Chronic lymphocytic leukemia is an immunocompromised blood cancer that can be treated with targeted agents like BTK inhibitors or BCL2 inhibitors, but currently there is no cure for the disease.
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
(2023)
Article
Medicine, Research & Experimental
Jani Huuhtanen, Mette Ilander, Bhagwan Yadav, Olli M. J. Dufva, Hanna Lahteenmaki, Tiina Kasanen, Jay Klievink, Ulla Olsson-Stromberg, Jesper Stentoft, Johan Richter, Perttu Koskenvesa, Martin Hoglund, Stina Soderlund, Arta Dreimane, Kimmo Porkka, Tobias Gedde-Dahl, Bjorn T. Gjertsen, Leif Stenke, Kristina Myhr-Eriksson, Berit Markevarn, Anna Lubking, Andreja Dimitrijevic, Lene Udby, Ole Weis Bjerrum, Henrik Hjorth-Hansen, Satu Mustjoki
Summary: In patients with chronic myeloid leukemia, combination therapy with dasatinib and IFN-alpha can improve deep molecular remission and restore immune function.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Oncology
Omar Elaskalani, Grace Gilmore, Madison Hagger, Ross I. Baker, Pat Metharom
Summary: This study investigates the mechanism of platelet dysfunction in chronic lymphocytic leukemia (CLL) patients and the impact of the new therapy ibrutinib. The presence of a CLL-derived factor called adenosine enhances the antiplatelet effects of ibrutinib. Further studies are needed to establish the correlation between adenosine, platelet function, and bleeding in CLL patients.
Article
Oncology
David Agdashian, Mei ElGindi, Changqing Xie, Milan Sandhu, Drew Pratt, David E. Kleiner, William D. Figg, Julie A. Rytlewski, Catherine Sanders, Erik C. Yusko, Bradford Wood, David Venzon, Gagandeep Brar, Austin G. Duffy, Tim F. Greten, Firouzeh Korangy
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2019)
Article
Multidisciplinary Sciences
Julie Rytlewski, Shibing Deng, Tao Xie, Craig Davis, Harlan Robins, Erik Yusko, Jadwiga Bienkowska
Meeting Abstract
Oncology
Arjun Khunger, Julie Rytlewski, Erik C. Yusko, Ahmad A. Tarhini
JOURNAL OF CLINICAL ONCOLOGY
(2019)
Article
Oncology
Arjun Khunger, Julie A. Rytlewski, Paul Fields, Erik C. Yusko, Ahmad A. Tarhini
Article
Multidisciplinary Sciences
Alexandre Reuben, Jiexin Zhang, Shin-Heng Chiou, Rachel M. Gittelman, Jun Li, Won-Chul Lee, Junya Fujimoto, Carmen Behrens, Xiaoke Liu, Feng Wang, Kelly Quek, Chunlin Wang, Farrah Kheradmand, Runzhe Chen, Chi-Wan Chow, Heather Lin, Chantale Bernatchez, Ali Jalali, Xin Hu, Chang-Jiun Wu, Agda Karina Eterovic, Edwin Roger Parra, Erik Yusko, Ryan Emerson, Sharon Benzeno, Marissa Vignali, Xifeng Wu, Yuanqing Ye, Latasha D. Little, Curtis Gumbs, Xizeng Mao, Xingzhi Song, Samantha Tippen, Rebecca L. Thornton, Tina Cascone, Alexandra Snyder, Jennifer A. Wargo, Roy Herbst, Stephen Swisher, Humam Kadara, Cesar Moran, Neda Kalhor, Jianhua Zhang, Paul Scheet, Ara A. Vaporciyan, Boris Sepesi, Don L. Gibbons, Harlan Robins, Patrick Hwu, John V. Heymach, Padmanee Sharma, James P. Allison, Veera Baladandayuthapani, Jack J. Lee, Mark M. Davis, Ignacio I. Wistuba, P. Andrew Futreal, Jianjun Zhang
NATURE COMMUNICATIONS
(2020)
Article
Hematology
Mark Leick, Rachel M. Gittelman, Erik Yusko, Catherine Sanders, Harlan Robins, Zachariah DeFilipp, Sarah Nikiforow, Jerome Ritz, Yi-Bin Chen
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
(2020)
Article
Hematology
Milos D. Miljkovic, Christopher Melani, Stefania Pittaluga, Rahul Lakhotia, Nicole Lucas, Allison Jacob, Erik Yusko, Elaine S. Jaffe, Wyndham H. Wilson, Mark Roschewski
Summary: Peripheral T-cell lymphomas (PTCLs) exhibit significant heterogeneity in terms of biology and clinical presentation, making treatment decisions challenging. This study showed that monitoring T-cell receptor (TCR) sequences using next-generation sequencing (NGS) identified tumor-specific clonotypes in PTCL patients undergoing frontline treatment. Patients with detectable ctDNA after therapy tended to have worse survival outcomes, indicating the potential utility of ctDNA as a prognostic marker in PTCL.
Article
Hematology
Rahul Lakhotia, Christopher Melani, Kieron Dunleavy, Stefania Pittaluga, Nakhle Saba, Liza Lindenberg, Esther Mena, Ethan Bergvall, Andrea Nicole Lucas, Allison Jacob, Erik Yusko, Seth M. Steinberg, Elaine S. Jaffe, Adrian Wiestner, Wyndham H. Wilson, Mark Roschewski
Summary: This study analyzed the dynamics of circulating tumor DNA (ctDNA) in patients with mantle cell lymphoma (MCL) following induction therapy. The results showed that patients with negative ctDNA after induction had longer survival, suggesting the potential of ctDNA as a prognostic biomarker. This supports further investigation into the use of ctDNA for response-adapted strategies in MCL.
Article
Cell Biology
Heather M. Callaway, Kathryn M. Hastie, Sharon L. Schendel, Haoyang Li, Xiaoying Yu, Jeremy Shek, Tierra Buck, Sean Hui, Dan Bedinger, Camille Troup, S. Moses Dennison, Kan Li, Michael D. Alpert, Charles C. Bailey, Sharon Benzeno, Jody L. Bonnevier, Jin-Qiu Chen, Charm Chen, Hyeseon Cho, Peter D. Crompton, Vincent Dussupt, Kevin C. Entzminger, Yassine Ezzyat, Jonathan K. Fleming, Nick Geukens, Amy E. Gilbert, Yongjun Guan, Xiaojian Han, Christopher J. Harvey, Julia M. Hatler, Bryan Howie, Chao Hu, Ailong Huang, Maya Imbrechts, Aishun Jin, Nik Kamachi, Gladys Keitany, Mark Klinger, Jay K. Kolls, Shelly J. Krebs, Tingting Li, Feiyan Luo, Toshiaki Maruyama, Michael A. Meehl, Letzibeth Mendez-Rivera, Andrea Musa, C. J. Okumura, Benjamin E. R. Rubin, Aaron K. Sato, Meiying Shen, Anirudh Singh, Shuyi Song, Joshua Tan, Jeffrey M. Trimarchi, Dhruvkumar P. Upadhyay, Yingming Wang, Lei Yu, Tom Z. Yuan, Erik Yusko, Bjoern Peters, Georgia Tomaras, Erica Ollmann Saphire
Summary: The SARS-CoV-2 Omicron variant and its sublineages are resistant to most therapeutic antibodies due to multiple mutations in the spike protein. However, 66 out of nearly 400 candidate therapeutics in the Coronavirus Immunotherapeutic Consortium (CoVIC) panel were found to neutralize Omicron and its sublineages in a neutralization assay. Most Omicron-neutralizing antibodies in natural immunoglobulin Gs (IgGs) recognize spike bivalently, while non-neutralizing IgGs either bind monovalently or have partial monovalent occupancy. Cleaving bivalent-binding IgGs to antigen-binding fragments (Fabs) abolishes neutralization and binding affinity, particularly against Omicron. These findings suggest that antibodies resistant to variant of concerns overcome mutations through avidity. Therefore, future SARS-CoV-2 vaccine strategies should consider trimeric spike epitope display with identical spacing and organization.
Meeting Abstract
Oncology
Rachel M. Gittelman, Mark Leick, Zachariah DeFilipp, Jerome Ritz, Erik Yusko, Catherine Sanders, Harlan Ro Bins
Correction
Oncology
Wiebke Pruessmann, Julie Rytlewski, James Wilmott, Martin C. Mihm, Grace H. Attrill, Beatrice Dyring-Andersen, Paul Fields, Qian Zhan, Andrew J. Colebatch, Peter M. Ferguson, John F. Thompson, Klaus Kallenbach, Erik Yusko, Rachael A. Clark, Harlan Robins, Richard A. Scolyer, Thomas S. Kupper
Article
Oncology
Wiebke Pruessmann, Julie Rytlewski, James Wilmott, Martin C. Mihm, Grace H. Attrill, Beatrice Dyring-Andersen, Paul Fields, Qian Zhan, Andrew J. Colebatch, Peter M. Ferguson, John F. Thompson, Klaus Kallenbach, Erik Yusko, Rachael A. Clark, Harlan Robins, Richard A. Scolyer, Thomas S. Kupper
Meeting Abstract
Oncology
Michael Pulsipher, Xia Han, Maire Quigley, Gabor Kari, Susana Rives, Theodore Laetsch, Gary Myers, Hidefumi Hiramatsu, Gregory Yanik, Muna Qayed, Timothy Driscoll, Michael Boyer, Heather Stefanski, Jochen Buchner, Andre Baruchel, Peter Bader, Lan Yi, Creton Kalfoglou, Harlan Robins, Erik Yusko, Gullu Gorgun, Eric Bleickardt, Stephane Wong, Stephan Grupp
PEDIATRIC BLOOD & CANCER
(2019)
Meeting Abstract
Oncology
Julie A. Rytlewski, Mark P. Rubinstein, Chadrick E. Delinger, Barry Gibney, Erik C. Yusko, Catherine Sanders, John M. Wrangle, Kathryn Lindsey
Meeting Abstract
Oncology
Michael A. Pulsipher, Xia Han, Maire Quigley, Gabor Kari, Susana Rives, Theodore W. Laetsch, Gary D. Myers, Hidefumi Hiramatsu, Gregory A. Yanik, Muna Qayed, Timothy Driscoll, Michael W. Boyer, Heather Stefanski, Jochen Buchner, Andre Baruchel, Peter Bader, Lan Yi, Creton Kalfoglou, Harlan Robins, Erik Yusko, Gullu Gorgun, Eric Bleickardt, Stephane Wong, Stephan A. Grupp