Review
Oncology
Md Ashik Ullah, Fabienne Mackay
Summary: B cell-activating factor (BAFF) and a proliferation-inducing ligand (APRIL) are members of the tumor necrosis factor (TNF) family, playing crucial roles in immune homeostasis and driving pathogenesis in autoimmunity and cancer. High levels of BAFF, APRIL, and their receptors are associated with disease severity and treatment response in different cancers. This review discusses the role of the BAFF-APRIL system in immune cell differentiation and tolerance, its pathogenic functions in hematological and solid cancers, and highlights emerging therapeutics targeting this system in various cancer types.
Article
Clinical Neurology
Samantha Ho, Eva Oswald, Hoi Kiu Wong, Atay Vural, Vuslat Yilmaz, Erdem Tuezuen, Recai Tuerkoglu, Tobias Straub, Ingrid Meinl, Franziska Thaler, Tania Kuempfel, Edgar Meinl, Simone Mader
Summary: In this study, the researchers found that anti-CD20 therapy can persistently deplete B cells and CD20(+) T cells in patients with multiple sclerosis. This therapy also reduces the levels of soluble TACI, which may enhance local APRIL activity and promote regulatory IgA(+) plasma cells and astrocytic IL-10 production.
NEUROLOGY-NEUROIMMUNOLOGY & NEUROINFLAMMATION
(2023)
Article
Immunology
Yasuhiro Shimojima, Dai Kishida, Takanori Ichikawa, Ryota Takamatsu, Shun Nomura, Yoshiki Sekijima
Summary: The features of circulating B cells in antineutrophil cytoplasmic antibody-associated vasculitis (AAV) were investigated. It was found that the proportion of B cells increased, expression of BAFF receptor decreased, and expression of TACI increased in AAV patients. Additionally, serum levels of BAFF and APRIL were elevated. These abnormalities persisted even in the remission phase of AAV, suggesting that abnormal signaling of BAFF and APRIL may contribute to disease relapse.
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
(2023)
Review
Immunology
Erik M. Matson, Miranda L. Abyazi, Kayla A. Bell, Kevin M. Hayes, Paul J. Maglione
Summary: CVID ILD, marked by pulmonary infiltration of T and B cells, is a common complication in CVID patients with poorly understood mechanisms. B cell depletive therapy has become a standard treatment, but questions regarding the timing and duration of treatment remain unanswered. Further research is needed to understand how dysregulated B cell biology contributes to ILD in CVID and improve diagnosis and management strategies.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Pathology
Michael D. Spinosa, William G. Montgomery, Melissa Lempicki, Prasad Srikakulapu, Matthew J. Johnsrude, Coleen A. McNamara, Gilbert R. Upchurch, Gorav Ailawadi, Norbert Leitinger, Akshaya K. Meher
Summary: The study demonstrated that BAFF antagonism can attenuate the formation and development of abdominal aortic aneurysm in mice. In the intervention group, BAFF antagonism reduced mature B-cell subsets, promoting resolution of inflammation in AAA tissues.
AMERICAN JOURNAL OF PATHOLOGY
(2021)
Article
Oncology
Lior Goldberg, Eric R. Haas, Vibhuti Vyas, Ryan Urak, Stephen J. Forman, Xiuli Wang
Summary: This study used mass cytometry to analyze the trafficking and functional protein expression of CD19 CAR-T cells in different tissues and revealed the spatiotemporal plasticity of CAR-T cells. The results showed significant alterations in the characteristics of CAR-T cells in different tissues, especially in the central nervous system niche.
Article
Hematology
Estelle Bourbon, Pierre Sesques, Morgane Gossez, Jeremie Tordo, Emmanuelle Ferrant, Violaine Safar, Florent Wallet, Guillaume Aussedat, Alizee Maarek, Fadhela Boua, Lionel Karlin, Dana Ghergus, Camille Golfier, Helene Lequeu, Anne Lazareth, Verane Schwiertz, Sebastien Viel, Maryam Idlhaj, Herve Ghesquieres, Guillaume Monneret, Emmanuel Bachy, Fabienne Venet
Summary: Despite the success of anti-CD19 CART cells in R/R LBCL, they are associated with toxicity and a high relapse rate. This study found that low HLA-DR expression on monocytes before CAR T-cell infusion is associated with older age, poorer performance status, higher tumor burden, and elevated inflammatory markers. Patients with low HLA-DR levels had a poorer duration of response and survival.
Article
Oncology
Yan Luo, Yaqing Qie, Martha E. Gadd, Alak Manna, Rocio Rivera-Valentin, Tommy To, Shuhua Li, Farah Yassine, Hemant S. Murthy, Roxana Dronca, Mohamed A. Kharfan-Dabaja, Hong Qin
Summary: This study developed a CAR-T cell therapy targeting B-cell activating factor receptor (BAFF-R) and demonstrated its antigen-specific cytotoxicity and antitumor effects against leukemia and lymphoma. The therapy specifically targeted BAFF-R expression in CLL and showed efficacy against CLL patient samples.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Article
Cell Biology
Nicola Schanda, Tim Sauer, Alexander Kunz, Angela Huckelhoven-Krauss, Brigitte Neuber, Lei Wang, Mandy Hinkelbein, David Sedloev, Bailin He, Maria-Luisa Schubert, Carsten Muller-Tidow, Michael Schmitt, Anita Schmitt
Summary: CAR-T cells are revolutionizing cancer immunotherapy and monitoring their expansion and persistence in patients is crucial. Flow cytometry and qPCR are effective methods for quality control of CAR-T cell products, with preference for CAR detection reagents with low background staining for monitoring CAR-T cell frequencies in patients.
Article
Immunology
Federica Dominelli, Maria Antonella Zingaropoli, Matteo Tartaglia, Eeva Tortellini, Mariasilvia Guardiani, Valentina Perri, Patrizia Pasculli, Federica Ciccone, Leonardo Malimpensa, Viola Baione, Anna Napoli, Aurelia Gaeta, Miriam Lichtner, Antonella Conte, Claudio Maria Mastroianni, Maria Rosa Ciardi
Summary: The study evaluated the humoral and specific T-cell response in people with MS under DMTs before and after vaccination. The results showed that DMTs may influence the immune response to vaccination in MS patients. The understanding of T-cell quality dynamic is important for determining the best vaccination strategy for MS patients under different DMTs.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Eirini Sevdali, Violeta Block Saldana, Matthaios Speletas, Hermann Eibel
Summary: BAFF receptor is a member of the TNF receptor family, expressed only by B cells and involved in regulating key signaling pathways essential for cellular functions. BAFFR deficiency can disrupt B cell development and impair immune responses. Polymorphisms in genes affecting BAFFR signaling have been linked to autoimmune diseases, immunodeficiency, and B cell lymphomas.
CURRENT OPINION IN IMMUNOLOGY
(2021)
Article
Oncology
Ekaterina Mikhailova, Olga Illarionova, Alexander Komkov, Elena Zerkalenkova, Ilgar Mamedov, Larisa Shelikhova, Yulia Olshanskaya, Natalia Miakova, Galina Novichkova, Alexander Karachunskiy, Michael Maschan, Alexander Popov
Summary: This study aimed to develop an antibody panel and data analysis algorithm for reliable minimal residual disease (MRD) detection in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) patients treated with CD19-directed therapy. The approach was adapted for possible CD19 loss and showed high qualitative concordance rates when compared to molecular techniques.
Review
Immunology
Massimiliano Gambella, Simona Carlomagno, Anna Maria Raiola, Livia Giannoni, Chiara Ghiggi, Chiara Setti, Chiara Giordano, Silvia Luchetti, Alberto Serio, Alessandra Bo, Michela Falco, Mariella Della Chiesa, Emanuele Angelucci, Simona Sivori
Summary: Surgical resection, chemotherapy, and radiotherapy have been the primary cancer treatments for a long time. Recently, immune checkpoint inhibitors and adoptive cell therapies have emerged as promising alternatives. These therapies aim to activate and utilize the patient's immune system to fight against cancer cells, and have shown remarkable results.
FRONTIERS IN IMMUNOLOGY
(2022)
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
Belen Blanco, Angel Ramirez-Fernandez, Clara Bueno, Lidia Argemi-Muntadas, Patricia Fuentes, Oscar Aguilar-Sopena, Francisco Gutierrez-Aguera, Samanta Romina Zanetti, Antonio Tapia-Galisteo, Laura Diez-Alonso, Alejandro Segura-Tudela, Maria Castella, Berta Marzal, Sergi Betriu, Seandean L. Harwood, Marta Compte, Simon Lykkemark, Ainhoa Erce-Llamazares, Laura Rubio-Perez, Anais Jimenez-Reinoso, Carmen Dominguez-Alonso, Maria Neves, Pablo Morales, Estela Paz-Artal, Sonia Guedan, Laura Sanz, Maria L. Toribio, Pedro Roda-Navarro, Manel Juan, Pablo Menendez, Luis Alvarez-Vallina
Summary: This study compares the efficacy of CAR-T19 cells and STAb-T19 cells and finds that STAb-T19 cells are more effective in inducing cytotoxicity, avoiding leukemia escape, and preventing relapse. CAR-T19 cells induce leukemia escape through rapid CD19 internalization and degradation, while STAb-T19 cells prevent CD19 downmodulation by forming canonical immunologic synapses. In a long-term patient-derived xenograft mouse model, STAb-T19 cells efficiently eradicate leukemia cells, while leukemia relapse occurs after CAR-T19 therapy.
CANCER IMMUNOLOGY RESEARCH
(2022)
