Review
Biochemistry & Molecular Biology
Paolo Sportoletti, Filomena De Falco, Beatrice Del Papa, Stefano Baldoni, Valerio Guarente, Andrea Marra, Erica Dorillo, Chiara Rompietti, Francesco Maria Adamo, Loredana Ruggeri, Mauro Di Ianni, Emanuela Rosati
Summary: Key features of CLL include immune system defects and leukemic cells’ ability to evade immune defenses, leading to increased susceptibility to infections and disease progression. The role of NK cells in CLL is less understood, but evidence suggests that NK cell dysfunctions in CLL mainly depend on escape mechanisms employed by leukemic cells. NK cells, with their preserved ADCC function and reversible dysfunctions, are an attractive source for novel immunotherapeutic strategies in CLL.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Geriatrics & Gerontology
Rongjiao Liu, Qizhi Luo, Weiguang Luo, Ling Wan, Quan Zhu, Xiangli Yin, Xiaofang Lu, Zixuan Song, Leiyan Wei, Zhiqing Xiang, Yizhou Zou
Summary: In this study, a soluble NKCAR was designed to trigger NK cell cytotoxicity by binding with the ligand MICA through the NKG2D receptor expressed on NK cells. The NKCAR showed bifunctional activity, recognizing both the CD20 antigen of target cells and the NKG2D receptor of NKL cells. The soluble NKCAR mediated the killing of CD20(+) Daudi cells in vitro, indicating its potential clinical application for killing target tumor cells.
Review
Immunology
Mercedes Beatriz Fuertes, Carolina Ines Domaica, Norberto Walter Zwirner
Summary: Immune checkpoint inhibitors have revolutionized immuno-oncology by achieving durable immune control of cancer, however, tumor immune evasion mechanisms pose a challenge for treatment development. Combination therapies targeting NK cell-activating receptors like NKG2D are emerging as frontrunners in immuno-oncology, with strategies to boost MICA/B expression and inhibit their shedding being proposed for enhancing antitumor immune responses.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Oncology
Max Yano, John C. Byrd, Natarajan Muthusamy
Summary: This article reviews the potential and progress of NK cell therapy for CLL, highlighting the immunosuppressive effects of CLL on NK cells as a major limitation to the development of effective treatments. Despite the challenges, NK cell therapy still holds significant therapeutic potential for CLL.
Review
Medicine, Research & Experimental
Zhenhui Wu, Huan Zhang, Min Wu, Guorui Peng, Yanqiu He, Na Wan, Yingjian Zeng
Summary: The NKG2D/NKG2D-L axis plays a crucial role in the development of AML, activating the immune system and affecting chemotherapy and immune recognition. Therefore, research targeting the NKG2D/NKG2D-L axis holds great potential for the discovery of novel biomacromolecule antibodies and pharmacological modulators.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Review
Medicine, Research & Experimental
Kerry A. Whalen, Kavya Rakhra, Naveen K. Mehta, Alexander Steinle, Jennifer S. Michaelson, Patrick A. Baeuerle
Summary: The field of immuno-oncology has revolutionized cancer patient care, but there are still challenges with current therapeutic approaches targeting T cells. Engaging the innate immune system, especially natural killer (NK) cells, has emerged as a promising modality in immunotherapy. This review focuses on therapeutic strategies that selectively engage NK cells for cancer therapy, particularly targeting the activating receptors NKG2D and CD16A.
Review
Oncology
Francesca Perutelli, Rebecca Jones, Valentina Griggio, Candida Vitale, Marta Coscia
Summary: Immune-based therapeutic strategies have revolutionized the treatment of hematological disorders by enhancing the immune response against tumor cells. However, individual use of immunotherapy has not shown optimal results in terms of disease control due to CLL-related immune dysfunctions. The understanding of the interactions between immune cells and tumor cells has led to the development of novel combination approaches that hold promise for future treatment of CLL.
FRONTIERS IN ONCOLOGY
(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)
Article
Oncology
Florencia Secchiari, Sol Yanel Nunez, Jessica Mariel Sierra, Andrea Ziblat, Maria Victoria Regge, Ximena Lucia Raffo Iraolagoitia, Agustin Rovegno, Carlos Ameri, Fernando Pablo Secin, Nicolas Richards, Hernando Rios Pita, Gonzalo Vitagliano, Luis Rico, Mauro Mieggi, Florencia Frascheri, Nicolas Bonanno, Leandro Blas, Aldana Trotta, Adrian David Friedrich, Mercedes Beatriz Fuertes, Carolina Ines Domaica, Norberto Walter Zwirner
Summary: NKG2D is an important activating receptor of natural killer (NK) cells that recognizes multiple ligands, including MICA. This study found that MICA is overexpressed in renal cell carcinoma (RCC) and is associated with decreased overall survival in RCC patients. Both tumor cells and tumor-infiltrating leukocytes showed increased MICA expression, while peripheral blood NK cells exhibited downregulated NKG2D. Furthermore, these NKG2D-expressing tumor-infiltrating NK cells displayed functional impairment and altered metabolic fitness.
Review
Oncology
Zeljko Todorovic, Dusan Todorovic, Vladimir Markovic, Nevena Ladjevac, Natasa Zdravkovic, Predrag Djurdjevic, Nebojsa Arsenijevic, Marija Milovanovic, Aleksandar Arsenijevic, Jelena Milovanovic
Summary: CAR T cell therapy has shown remarkable success in B-cell leukemia and lymphoma, but has had less success in chronic lymphocytic leukemia (CLL) patients. This review discusses the published results of CAR T cell therapy in CLL, possible mechanisms of failures, and expected developments in the field.
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
Multidisciplinary Sciences
Hui Ding, Garrett W. Buzzard, Sisi Huang, Michael G. Sehorn, R. Kenneth Marcus, Yanzhang Wei
Summary: The study created a fusion protein that combines the stress signal protein MICA to activate NK cells, and the G129R variant to target PRLR-positive breast cancer cells. This fusion protein can activate NK cells to kill PRLR-positive breast cancer cells and enhance the cytotoxicity of NK cells.
Review
Immunology
Elisavet Vlachonikola, Kostas Stamatopoulos, Anastasia Chatzidimitriou
Summary: Chronic lymphocytic leukemia remains incurable despite recent progress in management, highlighting the importance of further investigating the underlying pathophysiology. The interactions between malignant CLL cells and the tumor microenvironment play a crucial role in disease progression, with T cell abnormalities and potential therapeutic targets being a key focus in enhancing targeted cytotoxic activity against the malignant clone.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Cell Biology
Jagoda Siemaszko, Aleksandra Marzec-Przyszlak, Katarzyna Bogunia-Kubik
Summary: Natural Killer (NK) cells are natural cytotoxic cells of the innate immune system that can recognize and attack transformed or infected cells through their NKG2D receptor, which has significant immunological functions and clinical relevance.
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
Camila Guerrero, Noemi Puig, Maria-Teresa Cedena, Ibai Goicoechea, Cristina Perez, Juan-Jose Garces, Cirino Botta, Maria-Jose Calasanz, Norma C. Gutierrez, Maria-Luisa Martin-Ramos, Albert Oriol, Rafael Rios, Miguel-Teodoro Hernandez, Rafael Martinez-Martinez, Joan Bargay, Felipe de Arriba, Luis Palomera, Ana Pilar Gonzalez-Rodriguez, Adrian Mosquera-Orgueira, Marta-Sonia Gonzalez-Perez, Joaquin Martinez-Lopez, Juan-Jose Lahuerta, Laura Rosinol, Joan Blade, Maria-Victoria Mateos, Jesus F. San-Miguel, Bruno Paiva
Summary: This study established a comprehensive weighted model using machine learning algorithms to accurately predict undetectable measurable residual disease (MRD) outcomes in multiple myeloma patients, providing a new concept for personalized treatment.
CLINICAL CANCER RESEARCH
(2022)
Article
Medicine, Research & Experimental
Sara Gonzalez-Rodriguez, Seila Lorenzo-Herrero, Christian Sordo-Bahamonde, Agustin Hidalgo, Segundo Gonzalez, Luis Menendez, Ana Baamonde
Summary: The study found that CCL4-induced hyperalgesia is related to the desensitization of CCR5 in CD4(+) T-cells and to the release of IL-16 from CD8(+) lymphocytes.
Article
Oncology
Luis-Esteban Tamariz-Amador, Paula Rodriguez-Otero, Ana Jimenez-Ubieto, Laura Rosinol, Albert Oriol, Rafael Rios, Anna Sureda, Maria Jesus Blanchard, Miguel Teodoro Hernandez, Valentin Cabanas Perianes, Isidro Jarque, Juan Bargay, Mercedes Gironella, Felipe De Arriba, Luis Palomera, Yolanda Gonzalez-Montes, Josep M. Marti, Isabel Krsnik, Jose Maria Arguinano, Maria Esther Gonzalez, Luis Felipe Casado, Ana Pilar Gonzalez-Rodriguez, Lucia Lopez-Anglada, Noemi Puig, Maria Teresa Cedena, Bruno Paiva, Maria-Victoria Mateos, Jesus San-Miguel, Juan-Jose Lahuerta, Joan Blade, Inaki F. Troconiz
Summary: Response kinetics in multiple myeloma have been studied using a mathematical model to assess the prognostic value of serum monoclonal component (MC) response kinetics. The study identified two patient subgroups with significantly different progression-free survival based on the resistance parameter calculated by the model.
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2022)
Article
Oncology
Seila Lorenzo-Herrero, Christian Sordo-Bahamonde, Alejandra Martinez-Perez, Ma Daniela Corte-Torres, Ivan Fernandez-Vega, Ma Pilar Solis-Hernandez, Segundo Gonzalez
Summary: Glioblastoma is a common primary brain tumor, and immune checkpoint blockade strategies may offer a novel therapy for improving patient outcomes. ILT2 blockade has been found to promote an immune response against glioblastoma, and co-treatment with temozolomide enhances its efficacy.
Article
Oncology
Ana Villalba, Ana Pilar Gonzalez-Rodriguez, Javier Arzuaga-Mendez, Noemi Puig, Mario Arnao, Jose Maria Arguinano, Maria Jimenez, Marta Canet, Ana Teruel, Maria Sola, Francisco J. Diaz, Cristina Encinas, Antonio Garcia, Laura Rosinol, Alexia Suarez, Marta Sonia Gonzalez, Isabel Izquierdo, Miguel Teodoro Hernandez, Maria Stefania Infante, Maria Jose Sanchez, Antonia Sampol, Javier de la Rubia
Summary: This study suggests that tandem ASCT can improve the poor prognosis of patients with HR cytogenetic to some extent, which holds clinical significance for newly diagnosed patients with MM and HR cytogenetic.
LEUKEMIA & LYMPHOMA
(2022)
Article
Hematology
Carmen Martinez, Manuel Espeso de Haro, Samuel Romero, Antonio Gutierrez, Eva Domingo-Domenech, Ana P. Gonzalez-Rodriguez, Izaskun Zeberio, Maria Paz Martinez-Badas, Antonia Rodriguez-Izquierdo, Cecilia Carpio, Mariana Bastos-Oreiro, Jose Angel Hernandez-Rivas, Rolando Vallansot, Nicholas Kelleher, Francisco J. Diaz-Galvez, Tamara Torrado, Arturo Pereira, Ramon Garcia-Sanz
Summary: The AETHERA trial demonstrated that BV consolidation after ASCT can improve PFS in high-risk HL patients. BV is frequently used as front-line treatment and/or pre-ASCT salvage therapy. Real-life data analysis shows that BV consolidation can improve PFS regardless of BV exposure prior to ASCT.
ANNALS OF HEMATOLOGY
(2023)
Meeting Abstract
Hematology
Maria-Victoria Mateos, Joaquin Martinez-Lopez, Paula Rodriguez-Otero, Jesus San-Miguel, Veronica Gonzalez-Calle, Marta Sonia Gonzalez, Albert Oriol, Norma C. Gutierrez, Rafael Rios, Laura Rosinol Dachs, Miguel Angel Alvarez, Joan Bargay, Ana Pilar Gonzalez, Fernando Escalante, Adrian Alegre, Belen Inigo, Javier de la Rubia, Ana Isabel Teruel, Felipe De Arriba, Luis Palomera, Miguel-Teodoro Hernandez, Javier Lopez Jimenez, Marta Reinoso Segura, Aranzazu Garcia Mateo, Enrique M. Ocio, Joan Blade, Juan-Jose Lahuerta, Maria Teresa Cedena, Noemi Puig, Bruno Paiva
Editorial Material
Oncology
Alejandra Martinez-Perez, Candelaria Aguilar-Garcia, Segundo Gonzalez
Article
Oncology
Christian Sordo-Bahamonde, Seila Lorenzo-Herrero, Alejandra Martinez-Perez, Ana P. Gonzalez-Rodriguez, Angel R. Payer, Esther Gonzalez-Garcia, Candelaria Aguilar-Garcia, Sara Gonzalez-Rodriguez, Alejandro Lopez-Soto, Alejandra Garcia-Torre, Segundo Gonzalez
Summary: Patients with CLL show increased expression of inhibitory immune checkpoint BTLA on CD4+ and CD8+ T lymphocytes, leading to suppression of antitumor responses. Blocking BTLA enhances CD8+ T cell-mediated anti-leukemic responses, suggesting its potential as a therapeutic target in CLL.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Review
Oncology
Christian Sordo-Bahamonde, Seila Lorenzo-Herrero, Ana P. Gonzalez-Rodriguez, Alejandra Martinez-Perez, Juan P. Rodrigo, Juana M. Garcia-Pedrero, Segundo Gonzalez
Summary: Chemotherapy combined with immunotherapy, known as chemoimmunotherapy, is an emerging treatment option for cancer that aims to increase the efficacy of cancer treatment by targeting cancer cells and boosting the immune system's ability to fight cancer. Promising results have been observed in studies treating various types of cancer with chemoimmunotherapy, but further investigation is needed to determine the optimal dosing, timing, and sequencing of these treatments.
Article
Cell Biology
Diego Quintana-Torres, Alejandra Valle-Cao, Pablo Bousquets-Munoz, Sandra Freitas-Rodriguez, Francisco Rodriguez, Alejandro Lucia, Carlos Lopez-Otin, Alejandro Lopez-Soto, Alicia R. Folgueras
Summary: This study conducted a global plasma proteomic analysis in progeroid mouse models and found several upregulated proteins related to cardiovascular disease, the main cause of death in HGPS patients. The plasma proteome of progeroid mice exhibited an old signature, indicating accelerated aging. Furthermore, specific differences were observed in the circulating proteins between physiological and premature aging, highlighting potential biomarkers and therapeutic targets.
Meeting Abstract
Oncology
Borja Puertas, Veronica Gonzalez, Anna Sureda, Ma Jose Moreno, Albert Oriol, Ma Esther Gonzalez, Laura Rosinol, Jordi Lopez, Fernando Escalante, Joaquin Martinez Lopez, Estrella Carrillo, Esther Clavero, Ana Pilar Gonzalez Rodriguez, Victoria Dourdil, Felipe de Arriba de la Fuente, Marta Sonia Gonzalez, Jaime Perez de Oteyza, Miguel Teodoro Hernandez, Aranzazu Garcia Mateo, Joan Blade, Juan Jose Lahuerta Palacios, Jesus San-Miguel, Enrique Ocio, Maria-Victoria Mateos
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2022)
Meeting Abstract
Oncology
Ana Villalba, Pilar Lloret, Ana Pilar Gonzalez Rodriguez, Javier Arzuaga-Mendez, Noemi Puig, Mario Arnao, Jose Maria Arguinano, Maria Jimenez, Marta Canet, Ana I. Teruel, Maria Sola, Francisco J. Diaz, Cristina Encinas, Antonio Garcia, Laura Rosinol, Alexia Suarez, Marta Sonia Gonzalez, Isabel Izquierdo, Miguel Teodoro Hernandez, Maria Stefania Infante, Maria Jose Sanchez, Antonia Sampol, Javier De la Rubia
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2022)
Meeting Abstract
Biophysics
A. P. Gonzalez-Rodriguez, P. Palomo-Moraleda, J. Suarez-Paneda, J. Zanabili, S. Gonzalez-Muniz, L. R. Morais Bras, S. Lorenzo Herrero, C. Sordo-Bahamonde, A. Martinez-Perez, A. J. Gonzalez-Huerta
BONE MARROW TRANSPLANTATION
(2022)