Editorial Material
Immunology
Lisa Schmidleithner, Markus Feuerer
Summary: A recent study reveals that repression of Satb1 in CD4(+) T cells can drive intratumoral TLS formation, resulting in reduced tumor growth.
TRENDS IN IMMUNOLOGY
(2022)
Article
Immunology
Franziska Werner, Christine Wagner, Martin Simon, Katharina Glatz, Kirsten D. Mertz, Heinz Laeubli, Johannes Griss, Stephan N. Wagner
Summary: This study reveals that only a subgroup of primary human melanomas contain tertiary lymphoid structures (TLS), which rarely form germinal centers and mainly locate intratumorally within 1 mm distance to the invasive tumor front. In contrast, melanoma metastases have a significantly increased density of secondary follicular TLS, appearing preferentially in stromal areas within an extratumoral 1 mm distance to the invasive tumor front, with varying density over time and site of metastasis.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Urology & Nephrology
Yuki Sato, Karina Silina, Maries van den Broek, Kiyoshi Hirahara, Motoko Yanagita
Summary: Tertiary lymphoid structures (TLSs) are ectopic lymphoid tissues that drive antigen-specific immune responses at sites of chronic inflammation. Their presence correlates with disease course, with favorable outcomes in cancer and infection, but more severe disease in autoimmune and chronic inflammatory diseases. However, the mechanisms underlying these associations are still unclear.
NATURE REVIEWS NEPHROLOGY
(2023)
Article
Immunology
Jeremias G. Galletti, Kaitlin K. Scholand, Claudia M. Trujillo-Vargas, Zhiyuan Yu, Olivier Mauduit, Vanessa Delcroix, Helen P. Makarenkova, Cintia S. de Paiva
Summary: Aging is a complex biological process that affects multiple organs. In this study, the authors investigated the changes in the immune landscape of aged lacrimal glands (LGs) in mice. They found increased lymphoid infiltrates and ectopic lymphoid structures in aged LGs, as well as alterations in B and T cell populations and gene expression associated with immune activation and germinal center formation. These findings indicate a profound change in the immune response of aged LGs, with B cells becoming predominant.
CLINICAL IMMUNOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Girija Goyal, Pranav Prabhala, Gautam Mahajan, Bruce Bausk, Tal Gilboa, Liangxia Xie, Yunhao Zhai, Roey Lazarovits, Adam Mansour, Min Sun Kim, Aditya Patil, Danielle Curran, Jaclyn M. Long, Sanjay Sharma, Abidemi Junaid, Limor Cohen, Thomas C. Ferrante, Oren Levy, Rachelle Prantil-Baun, David R. Walt, Donald E. Ingber
Summary: In this study, researchers successfully cultured human ectopic lymphoid follicles with similar characteristics to lymphoid follicles in a microfluidic chip. These follicles showed improved immune responses to vaccines and can serve as an alternative to non-human primates for preclinical evaluation.
Review
Immunology
Charlotte Domblides, Juliette Rochefort, Clemence Riffard, Marylou Panouillot, Geraldine Lescaille, Jean-Luc Teillaud, Veronique Mateo, Marie-Caroline Dieu-Nosjean
Summary: The tumor microenvironment is unique to each patient and therapies targeting tumor cells or immune cells have limited long-term benefits. Hot tumors play a role in selecting therapies targeting patient immunity, with the presence of TLS associated with better survival and predicted response to ICP inhibitors. Increasing understanding of TLS biology may improve prognostic prediction and treatment selection for cancer patients.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Wendi Kang, Zhichao Feng, Jianwei Luo, Zhenhu He, Jun Liu, Jianzhen Wu, Pengfei Rong
Summary: TLSs play a vital role in the tumor microenvironment and are closely associated with favorable clinical outcomes in most types of cancers, though there are some studies reporting an association with a poor prognosis. Further investigation into their double-edged sword role and potential mechanisms is needed to provide novel therapeutic perspectives for antitumor immunoregulation.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Dessislava Malinova, Laabiah Wasim, Rebecca Newman, Ana Martinez-Riano, Niklas Engels, Pavel Tolar
Summary: The research identified the crucial role of B-cell endosomal trafficking pathways in regulating antigen uptake, B-cell proliferation, and antibody responses, especially in germinal center B-cell reactions and high-affinity antibody production.
Article
Chemistry, Multidisciplinary
Feng Li, Zhou Liang, Haojie Zhong, Xinrong Hu, Ziwen Tang, Changjian Zhu, Jiani Shen, Xu Han, Ruoni Lin, Ruilin Zheng, Ruihan Tang, Huajing Peng, Xunhua Zheng, Chengqiang Mo, Peisong Chen, Xin Wang, Qiong Wen, Jianbo Li, Xi Xia, Hongjian Ye, Yagui Qiu, Jianwen Yu, Dongying Fu, Jiaqi Liu, Rong Wang, Huixin Xie, Yun Guo, Xiaoyan Li, Jinjin Fan, Qinghua Liu, Haiping Mao, Wei Chen, Yi Zhou
Summary: In lupus nephritis (LN), gut-derived group 3 innate lymphoid cells (ILC3s) migrate from the small intestine to the kidney via the CXCR6/CXCL16 axis, contributing to the progression of LN, including spleen and lymph node enlargement, antibody production, and renal injury. In renal ectopic lymphoid structures (ELS), ILC3s induce B cell activation in a Delta-like1 (DLL1)/Notch-dependent manner, accompanied by up-regulation of Deltex1 and MAML1.
Article
Oncology
Andrew J. Gunderson, Venkatesh Rajamanickam, Cynthia Bui, Brady Bernard, Joanna Pucilowska, Carmen Ballesteros-Merino, Mark Schmidt, Kayla McCarty, Michaela Philips, Brian Piening, Christopher Dubay, Terry Medler, Phillipa Newell, Paul Hansen, Eric Tran, Ephraim Tang, Carlo Bifulco, Marka Crittenden, Michael Gough, Kristina H. Young
Summary: PDAC tumors show T cell inflamed phenotypes, with some tumors having early-stage TLS which correlates with higher survival rates.
Article
Immunology
Thomas J. Lynch, Bethany A. Ahlers, Anthony M. Swatek, Vitaly Ievlev, Albert C. Pai, Leonard Brooks, Yinghua Tang, Idil A. Evans, David K. Meyerholz, John F. Engelhardt, Kalpaj R. Parekh
Summary: This study utilized a ferret transplantation model to investigate the characteristics and pathogenesis of obliterative bronchiolitis (OB) and restrictive alveolar fibroelastosis (AFE) in chronic lung allograft dysfunction (CLAD). The results showed that both OB and AFE allografts developed tertiary lymphoid organs (TLOs), but AFE had larger and more abundant TLOs. The expression of B-cell lymphoma 6 Transcription Repressor (BCL-6) and forkhead box P3 were associated with AFE, along with higher levels of immunoglobulins, plasma cells, and complement 4d. This study provides valuable insights into the factors contributing to OB and AFE, and may guide the development of immunomodulatory and antifibrotic therapies for lung transplant patients.
Article
Multidisciplinary Sciences
Luuk van Hooren, Alessandra Vaccaro, Mohanraj Ramachandran, Konstantinos Vazaios, Sylwia Libard, Tiarne van de Walle, Maria Georganaki, Hua Huang, Ilkka Pietilae, Joey Lau, Maria H. Ulvmar, Mikael C. I. Karlsson, Maria Zetterling, Sara M. Mangsbo, Asgeir S. Jakola, Thomas Olsson Bontell, Anja Smits, Magnus Essand, Anna Dimberg
Summary: This study demonstrates that the use of immunostimulatory CD40 antibodies in glioma models promotes the formation of tertiary lymphoid structures but does not improve survival and impairs the response to immune checkpoint blockade.
NATURE COMMUNICATIONS
(2021)
Article
Rheumatology
E. Carlotti, W. Murray-Brown, K. Blighe, M. Caliste, E. Astorri, N. Sutcliffe, A. R. Tappuni, C. Pitzalis, E. Corsiero, M. Bombardieri
Summary: This study reveals the clonal diversification and recirculation of autoreactive B cells in ectopic germinal centers in Sjogren's syndrome, which may explain the difficulty in eradicating ectopic germinal centers in the treatment of the syndrome.
CLINICAL AND EXPERIMENTAL RHEUMATOLOGY
(2022)
Article
Oncology
Natalie S. Firmino, Rachel A. Cederberg, Che-Min Lee, Rocky Shi, Brennan J. Wadsworth, S. Elizabeth Franks, Kiersten N. Thomas, Lisa R. Decotret, Kevin L. Bennewith
Summary: The study showed that tumor-reactive germinal centers (GCs) exhibit hypoxia, which negatively regulates tumor-induced humoral immune responses. GC hypoxia is associated with levels of antibody-secreting B cells and impairs B cell proliferation and class-switching in vitro.
Article
Cell Biology
Lingyun Li, Chunlei Feng, Jun Qin, Dali Li, Mingyao Liu, Shuhua Han, Biao Zheng
Summary: The study reveals the crucial role of HIF-1 alpha in regulating humoral immunity through metabolic reprogramming in GC B-cells, with deficiency impairing the functional GC response and affecting the generation of high-affinity plasma cells. This newly discovered metabolic characteristic of GC B-cells will enhance understanding of GC biology and B-cell lymphomagenesis.
CELLULAR IMMUNOLOGY
(2021)
