Article
Multidisciplinary Sciences
Zohreh Amoozgar, Jonas Kloepper, Jun Ren, Rong En Tay, Samuel W. Kazer, Evgeny Kiner, Shanmugarajan Krishnan, Jessica M. Posada, Mitrajit Ghosh, Emilie Mamessier, Christina Wong, Gino B. Ferraro, Ana Batista, Nancy Wang, Mark Badeaux, Sylvie Roberge, Lei Xu, Peigen Huang, Alex K. Shalek, Dai Fukumura, Hye-Jung Kim, Rakesh K. Jain
Summary: In this study, researchers found that treatment with an agonistic anti-GITR antibody converts tumor infiltrating regulatory T cells to effector cells, overcoming resistance to PD1 blockade in preclinical models of GBM.
NATURE COMMUNICATIONS
(2021)
Article
Pharmacology & Pharmacy
O. Y. Balcik, D. Akin, G. S. Ceylan, B. Demir, A. Aytac, N. Culhaci, E. Oktay
Summary: In patients with metastatic RCC, higher GITR levels are associated with better progression-free survival (PFS), particularly in patients treated with nivolumab. Therefore, GITR may serve as both a prognostic and predictive marker.
EUROPEAN REVIEW FOR MEDICAL AND PHARMACOLOGICAL SCIENCES
(2023)
Article
Medicine, General & Internal
Kuebra Kaban, Sarah M. Greiner, Samuel Holzmayer, Claudia Tandler, Sophie Meyer, Clemens Hinterleitner, Helmut R. Salih, Melanie Maerklin, Jonas S. Heitmann
Summary: Novel therapies have improved treatment of CLL patients, but multiple treatment regimes are still required. Evaluating the relevance of GITR/4-1BB and their ligands for CLL prognosis, high levels of 4-1BB on leukemic cells were associated with significantly shorter survival, identifying it as a prognostic marker for CLL.
Review
Immunology
Kai Yang
Summary: Regulatory T cells (Tregs) play important roles in immune regulation, and cellular metabolism is crucial for their function. Tregs reprogram cellular metabolic programs to sustain their suppressive function, and altered metabolism also influences Treg activation and function. Manipulation of systemic metabolites has emerged as an attractive strategy to modulate tissue Treg metabolism and improve treatment of immune-related diseases.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Alex Yashchenko, Sarah J. Bland, Cheng J. Song, Ummey Khalecha Bintha Ahmed, Rachel Sharp, Isabella G. Darby, Audrey M. Cordova, Morgan E. Smith, Jeremie M. Lever, Zhang Li, Ernald J. Aloria, Shuja Khan, Bibi Maryam, Shanrun Liu, Michael R. Crowley, Kenneth L. Jones, Lauren A. Zenewicz, James F. George, Michal Mrug, David K. Crossman, Katharina Hopp, Stavros Stavrakis, Mary B. Humphrey, Florent Ginhoux, Kurt A. Zimmerman
Summary: Kidney macrophages in healthy mice exhibit cellular heterogeneity, with four major subsets of monocytes and two major subsets of kidney resident macrophages. The expression of Ccr2 in kidney resident macrophages is not solely derived from Ly6c(hi) monocytes, and Ccr2 expression reflects their spatial distribution in the kidney cortex. The gene Cx3cr1 regulates the heterogeneity of kidney resident macrophages and plays a role in niche-specific disease progression.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Cell Biology
Huisi Liu, Weiwei Wu, Gangyu Sun, Tiongsun Chia, Lei Cao, Xiaodan Liu, Jian Guan, Fenggen Fu, Ying Yao, Zhihai Wu, Shuaixiang Zhou, Jie Wang, Jia Lu, Zhihui Kuang, Min Wu, Luan He, Zhiyuan Shao, Dongdong Wu, Bingliang Chen, Wenqing Xu, Zhizhi Wang, Kaijie He
Summary: This study presents a potent Fc gamma R-independent GITR agonist IBI37G5 that can effectively activate effector T cells and synergize with anti-PD1 antibody. The antibody self-competition and the unique antibody-receptor stoichiometry required for GITR activation are also analyzed. Furthermore, an alternative dose-finding strategy based on RO-function relations is proposed for the clinical translation of GITR and similar co-stimulatory agonists.
CELL REPORTS MEDICINE
(2022)
Article
Oncology
Tatiana Hernandez-Guerrero, Victor Moreno
Summary: Glucocorticoid-induced TNF receptor (TNFR)-related protein (GITR) agonistic antibodies enhance the antitumor response by reducing the effect of Foxp3+ T-regulatory cells. However, the novel GITR agonist TRX-518 has shown limited clinical activity in patients with advanced solid tumors.
CLINICAL CANCER RESEARCH
(2022)
Article
Medicine, General & Internal
Igor Kudryavtsev, Yulia Zinchenko, Anna Starshinova, Maria Serebriakova, Anna Malkova, Tatiana Akisheva, Dmitriy Kudlay, Anzhela Glushkova, Piotr Yablonskiy, Yehuda Shoenfeld
Summary: This study aimed to evaluate the distribution and disturbance of circulating Treg cell subsets in patients with sarcoidosis. The results showed a decrease in the absolute numbers of Treg cells and several alterations in Treg cell subsets in patients with sarcoidosis. These findings suggest that the balance of Treg cell populations could be used for the diagnosis and prognosis of sarcoidosis.
Article
Immunology
Ruijing Zhang, Keman Xu, Ying Shao, Yu Sun, Jason Saredy, Elizabeth Cutler, Tian Yao, Ming Liu, Lu Liu, Charles Drummer, Yifan Lu, Fatma Saaoud, Dong Ni, Jirong Wang, Yafeng Li, Rongshan Li, Xiaohua Jiang, Hong Wang, Xiaofeng Yang
Summary: Through studying the transcriptomic heterogeneity of Treg in different tissues, we found shared genes, signaling pathways, and immune functions, providing novel therapeutic targets for immune system diseases and cancer.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Cell Biology
Armin Sadeghi, Safa Tahmasebi, Arshad Mahmood, Maria Kuznetsova, Hamed Valizadeh, Ali Taghizadieh, Masoud Nazemiyeh, Leili Aghebati-Maleki, Farhad Jadidi-Niaragh, Sanaz Abbaspour-Aghdam, Leila Roshangar, Haleh Mikaeili, Majid Ahmadi
Summary: In COVID-19 patients, an increase in Th17 cells and decrease in Treg cells are associated with hyperinflammation and disease progression, with a higher inflammatory ratio observed in deceased patients compared to those who improved, indicating the critical role of inflammation in patient mortality.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Article
Immunology
Tania Sarkar, Subhanki Dhar, Dwaipayan Chakraborty, Subhadip Pati, Sayantan Bose, Abir K. Panda, Udit Basak, Sourio Chakraborty, Sumon Mukherjee, Aharna Guin, Kuladip Jana, Diptendra K. Sarkar, Gaurisankar Sa
Summary: Tumor-infiltrating T-regulatory cells play a significant role in immunotherapy resistance, and the chemokine receptor CCR4 is involved in regulating their infiltration. The transcription activator FOXP3 not only activates CCR4 but also regulates T-regulatory cell infiltration in the tumor microenvironment. Genetic ablation of FOXP3 reduces tumor size and restores anti-tumor immunity, while overexpression of FOXP3 increases tumor infiltration and progression.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Zhan Xu, Xue Jiang, Xueyu Dai, Bin Li
Summary: The COVID-19 pandemic has caused severe global impact, with activated immune response as a key feature. Regulatory T cells play a crucial role in suppressing inflammatory response and tissue repair. Research on the changes of FOXP3(+) Tregs in COVID-19 patients, their relationship with disease severity, and the potential role of FOXP3(+) Tregs in SARS-CoV-2 infection are discussed.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Simon Borna, Beruh Dejene, Uma Lakshmanan, Janika Schulze, Kenneth Weinberg, Rosa Bacchetta
Summary: The Chromosome 22q11.2 deletion syndrome (22q11.2DS) leads to an innate immune system error, including thymic hypoplasia, reduced T lymphocyte output, immunodeficiency, and increased incidence of autoimmune diseases. A previous study suggested a defect in the regulatory T cells (Treg) cell lineage commitment in the thymus of patients with 22q11.2DS. However, our study found no significant differences in the frequencies and basic phenotype of Treg cells at each developmental stage in 22q11.2DS patients.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Feng Wang, Bryant Chau, Sean M. West, Christopher R. Kimberlin, Fei Cao, Flavio Schwarz, Barbara Aguilar, Minhua Han, Winse Morishige, Christine Bee, Gavin Dollinger, Arvind Rajpal, Pavel Strop
Summary: Glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) and GITR ligand (GITRL) are members of the tumor necrosis superfamily that regulate immune cell activities, including anti-tumor immune responses. The structures and visualization of human and mouse GITR-GITRL complexes provide insights into the architecture of higher-order membrane assemblies and their signaling mechanisms.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Minmin Lu, Wenli Zhao, Shuo Han, Xiaowen Lin, Tingyu Xu, Qiuxiang Tan, Mu Wang, Cuiying Yi, Xiaojing Chu, Weibo Yang, Ya Zhu, Beili Wu, Qiang Zhao
Summary: CX3CR1, as the receptor of CX3CL1, has potential therapeutic significance in diseases, but drug development is hindered by lack of structural information. Studies reveal that CX3CR1 shows minimal conformational changes upon activation, possibly linked with the role of cholesterol molecules.
Article
Immunology
Yuejin Liang, Zuliang Jie, Lifei Hou, Panpan Yi, Wei Wang, Zakari Kwota, Maria Salvato, Rene de Waal Malefyt, Lynn Soong, Jiaren Sun
EUROPEAN JOURNAL OF IMMUNOLOGY
(2015)
Article
Multidisciplinary Sciences
Louise Sjokvist Ottsjo, Carl-Fredrik Flach, Staffan Nilsson, Rene de Waal Malefyt, Anna K. Walduck, Sukanya Raghavan
Article
Biochemical Research Methods
Xuemei Zhao, Gulesi Ayanoglu, Melissa Bilardello, Laurence Fayadat-Dilman, Jeffrey H. Zhang, Hai Ling Li, Laura Bald, Terri Mcclanahan, Rene de Waal Malefyt, Russell Weiner, Omar F. Laterza
Article
Immunology
Juhan Yoon, Juan Manuel Leyva-Castillo, Guoxing Wang, Claire Galand, Michiko K. Oyoshi, Lalit Kumar, Sabine Hoff, Rui He, Alexander Chervonsky, Joost J. Oppenheim, Vijay K. Kuchroo, Marcel R. M. van den Brink, Rene De Waal Malefyt, Philippe A. Tessier, Robert Fuhlbrigge, Philip Rosenstiel, Cox Terhorst, George Murphy, Raif S. Geha
JOURNAL OF EXPERIMENTAL MEDICINE
(2016)
Article
Immunology
Mayya Geha, Maria G. Tsokos, Robin E. Bosse, Tatyana Sannikova, Yoichiro Iwakura, Jurandir J. Dalle Lucca, Rene De Waal Malefyt, George C. Tsokos
JOURNAL OF IMMUNOLOGY
(2017)
Article
Biochemical Research Methods
Bhagyashree Bhagwat, Holly Cherwinski, Manjiri Sathe, Wolfgang Seghezzi, Terrill K. McClanahan, Rene de Waal Malefyt, Aarron Willingham
JOURNAL OF IMMUNOLOGICAL METHODS
(2018)
Article
Anatomy & Morphology
Novica M. Milicevic, Ivana M. Lalic, Sanja Z. Despotovic, Darko N. Ciric, Jurgen Westermann, Rene De Waal Malefyt, Zivana Milicevic
ANATOMICAL RECORD-ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY
(2014)
Article
Rheumatology
Iannis E. Adamopoulos, Erika Suzuki, Cheng-Chi Chao, Dan Gorman, Sarvesh Adda, Emanual Maverakis, Konstantinos Zarbalis, Richard Geissler, Agelio Asio, Wendy M. Blumenschein, Terrill Mcclanahan, Rene De Waal Malefyt, M. Eric Gershwin, Edward P. Bowman
ANNALS OF THE RHEUMATIC DISEASES
(2015)
Article
Biochemistry & Molecular Biology
Gongxian Liao, Boaz van Driel, Erica Magelky, Michael S. O'Keeffe, Rene de Waal Malefyt, Pablo Engel, Roland W. Herzog, Emiko Mizoguchi, Atul K. Bhan, Cox Terhorst
Article
Immunology
David Bauche, Barbara Joyce-Shaikh, Renu Jain, Jeff Grein, Karin S. Ku, Wendy M. Blumenschein, Stephanie C. Ganal-Vonarburg, Douglas C. Wilson, Terrill K. McClanahan, Rene de Waal Malefyt, Andrew J. Macpherson, Lakshmanan Annamalai, Jennifer H. Yearley, Daniel J. Cua
Article
Multidisciplinary Sciences
Prasanna M. Chandramouleeswaran, Dawen Shen, Anna J. Lee, Alain Benitez, Kara Dods, Fiona Gambanga, Benjamin J. Wilkins, Jamie Merves, Yuliana Noah, Sarit Toltzis, Jennifer H. Yearley, Jonathan M. Spergel, Hiroshi Nakagawa, Rene deWaal Malefyt, Amanda B. Muir, Mei-Lun Wang
Article
Multidisciplinary Sciences
Joerg Ermann, Tracy Staton, Jonathan N. Glickman, Rene de Waal Malefyt, Laurie H. Glimcher
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2014)
Article
Cell Biology
Paul-Joseph Aspuria, Sandro Vivona, Michele Bauer, Marie Semana, Navneet Ratti, Scott McCauley, Romina Riener, Rene de Waal Malefyt, Deepti Rokkam, Jan Emmerich, Rob A. Kastelein, Patrick J. Lupardus, Martin Oft
Summary: CAR-T cells show durable responses in refractory hematological tumors, but effective control of CAR-T cell population is crucial to prevent tumor progression. An orthogonal IL-2 receptor/ligand system provides specific in vivo control of CAR-T cell expansion and activation, enhancing efficacy of CAR-T therapies.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Letter
Allergy
Ben Nicholas, Jane Guo, Hyun-Hee Lee, Alistair Bailey, Rene de Waal Malefyt, Milenko Cicmil, Ratko Djukanovic
CLINICAL AND EXPERIMENTAL ALLERGY
(2022)