Review
Oncology
Anne B. C. Cherry, Nicholas A. Gherardin, Hafiz I. Sikder
Summary: This minireview explores the biology of gamma delta T cells, including their unique ability to recognize intracellular disturbances and non-peptide-based antigens, and proposes a framework for understanding gamma delta T cell-inspired therapeutic strategies in cancer treatment.
FRONTIERS IN ONCOLOGY
(2022)
Article
Immunology
Marta Sanz, Brendan T. Mann, Paul L. Ryan, Alberto Bosque, Daniel J. Pennington, Holger Hackstein, Natalia Soriano-Sarabia
Summary: Under non-pathological conditions, human ?d T cells represent a small fraction of CD3(+) T cells in peripheral blood (1-10%). They constitute a unique subset of T lymphocytes that recognize stress ligands or non-peptide antigens through MHC-independent presentation. Major human ?d T cell subsets, Vd1 and Vd2, expand in response to microbial infection or malignancy, but possess distinct tissue localization, antigen recognition, and effector responses. By comparing highly purified Vd1 and Vd2 cells, this study found distinct genetic and phenotypic signatures that define functional differences in ?d T cell populations, suggesting that Vd1 and Vd2 T cells are different lineages. These findings will facilitate further investigation into the ligand specificity and unique role of Vd1 and Vd2 cells in early immune responses.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Yingping Xu, Peter Dimitrion, Steven Cvetkovski, Li Zhou, Qing-Sheng Mi
Summary: DETCs are a unique and conserved population of gamma delta T cells enriched in the epidermis, serving as regulators of immune responses and sense skin injury. Despite advances in understanding their development and function, the origin and underlying molecular mechanisms remain elusive.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Review
Immunology
Guanyu Qu, Shengli Wang, Zhenlong Zhou, Dawei Jiang, Aihua Liao, Jing Luo
Summary: This article summarizes the current knowledge of the γδT cell phenotype in various tissues in mice and humans, describing the similarities and differences of tissue-resident γδT cells in these two species.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Edith M. Walker, Kristen M. Merino, Nadia Slisarenko, Brooke F. Grasperge, Smriti Mehra, Chad J. Roy, Deepak Kaushal, Namita Rout
Summary: This study explored the immune responses of unconventional lipid-reactive T cells following BCG inoculation and SIV infection. The results showed that BCG exposure increased the frequency of BAL gamma delta T cells and induced both systemic and local Th1-type response. SIV infection led to a decline in IL-7R expression and IFN-gamma production in gamma delta T cells, but their cytolytic potential was maintained. These findings contribute to a deeper understanding of the functions of lipid-reactive T cells and may provide new approaches to enhance TB control.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Shengdong Wang, Hengyuan Li, Tao Chen, Hao Zhou, Wenkan Zhang, Nong Lin, Xiaohua Yu, Yu Lou, Binghao Li, Eloy Yinwang, Zenan Wang, Keyi Wang, Yucheng Xue, Hao Qu, Peng Lin, Hangxiang Sun, Wangsiyuan Teng, Haochen Mou, Xupeng Chai, Zhijian Cai, Zhaoming Ye
Summary: In this study, activated V gamma 9V delta 2 T cells were found to induce strong CD8(+) T cell responses in osteosarcoma cells and effectively suppress osteosarcoma growth in xenograft animal models. Mechanistically, activated gamma delta T cells exhibited increased HSP90 production, which upregulated MyD88 and activated JNK, leading to enhanced CD8(+) T cell cross-priming through increased CCL5 secretion. These findings suggest that V gamma 9V delta 2 T cells may serve as a promising alternative antigen-presenting cell (APC) for the development of gamma delta T cell-based tumor immunotherapy.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Article
Immunology
Xiaofeng Mu, Zheng Xiang, Yan Xu, Jing He, Jianwen Lu, Yuyuan Chen, Xiwei Wang, Chloe Ran Tu, Yanmei Zhang, Wenyue Zhang, Zhinan Yin, Wing-hang Leung, Yu-Lung Lau, Yinping Liu, Wenwei Tu
Summary: Patients with type 2 diabetes mellitus have an increased risk of cancer, with dysregulated glucose metabolism potentially impairing the anticancer activity of immune cells. Restoring AMPK pathway through metformin treatment may improve tumor immunosurveillance.
CELLULAR & MOLECULAR IMMUNOLOGY
(2022)
Article
Immunology
Marco A. Ataide, Konrad Knoepper, Paulina Cruz de Casas, Milas Ugur, Sarah Eickhoff, Mangge Zou, Haroon Shaikh, Apurwa Trivedi, Anika Grafen, Tao Yang, Immo Prinz, Knut Ohlsen, Mercedes Gomez de Agueero, Andreas Beilhack, Jochen Huehn, Mauro Gaya, Antoine-Emmanuel Saliba, Georg Gasteiger, Wolfgang Kastenmueller
Summary: This study found that tissue-derived unconventional T cells migrate through the lymphatic route to locally draining lymph nodes, resulting in distinct populations of cells in each lymph node. These cells cooperate in immune responses and differ between lymph nodes that drain different tissues.
Review
Oncology
Derek Lee, Carl J. Rosenthal, Natalie E. Penn, Zachary Spencer Dunn, Yang Zhou, Lili Yang
Summary: γδ (gamma delta) T cells are a minor population of T cells with both innate and adaptive immune properties. They can be activated independently of MHC, making them ideal for immunotherapy development. Gene editing technologies can enhance the antitumor functions of different subsets of γδ T cells.
Article
Immunology
Hannah Kaminski, Coline Menard, Bouchra El Hayani, And-Nan Adjibabi, Gabriel Marseres, Maxime Courant, Atika Zouine, Vincent Pitard, Isabelle Garrigue, Sonia Burrel, Jean-Francois Moreau, Lionel Couzi, Jonathan Visentin, Pierre Merville, Julie Dechanet-Merville
Summary: V gamma 9(neg)V delta 2(pos) T cells are identified as key effectors in the immune response against CMV, exhibiting significant cytotoxic potential and activation capabilities. In transplant recipients with CMV infection, the expansion of these cells is closely associated with disease severity.
JOURNAL OF INFECTIOUS DISEASES
(2021)
Article
Immunology
Gitte Holmen Olofsson, Manja Idorn, Ana Micaela Carnaz Simoes, Pia Aehnlich, Signe Koggersbol Skadborg, Elfriede Noessner, Reno Debets, Bernhard Moser, Ozcan Met, Per Thor Straten
Summary: Human Vγ9Vδ2 T cells expanded in vitro efficiently kill cancer cells, have the ability to cross-present MHC class I-restricted peptides, and support tumor-specific CD8 T cell responses.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Rebecca L. O'Brien, Jennifer Matsuda, M. Kemal Aydintug, Niyun Jin, Swati Phalke, Willi K. Born
Summary: Previous studies have shown inconsistent results regarding the role of gamma delta T cells in the development of type 1 diabetes. This study focused on NOD mice and found that NOD V γ4+ γδ T cells inhibit diabetes development, while NOD V γ1+ cells promote it. Additionally, changes in the abundance of other T cell types were observed in NOD mice deficient in specific gamma delta T cell subsets.
Review
Immunology
Qiuting Zhang, Miao Xu
Summary: This article summarizes T-cell responses in EBV-related cancers, considering latency patterns, host immune status, and factors such as human leukocyte antigen (HLA) susceptibility that may affect immune outcomes. The authors also discuss the potential roles of EBV-specific T-cell responses in tumor microenvironments and describe T-cell immunotherapy strategies that harness EBV antigens.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Shi-Wei Huang, Chih-Ming Pan, Yu-Chuan Lin, Mei-Chih Chen, Yeh Chen, Chia-Ing Jan, Chung-Chun Wu, Fang-Yu Lin, Sin-Ting Wang, Chen-Yu Lin, Pei-Ying Lin, Wei-Hsaing Huang, Yu-Ting Chiang, Wan-Chen Tsai, Ya-Hsu Chiu, Ting-Hsun Lin, Shao-Chih Chiu, Der-Yang Cho
Summary: HLA-G is an immune checkpoint protein and a tumor-associated antigen. Previous research has shown the potential of using CAR-NK targeting HLA-G to treat certain solid tumors. However, co-expression of PD-L1 and HLA-G and up-regulation of PD-L1 after immunotherapy may reduce the effectiveness of HLA-G-CAR. Therefore, a multi-specific CAR targeting both HLA-G and PD-L1 could provide a solution.
Article
Immunology
Eline van Diest, Mara J. T. Nicolasen, Lovro Kramer, Jiali Zheng, Patricia Hernandez-Lopez, Dennis X. Beringer, Jurgen Kuball
Summary: In this study, we developed a novel T cell engager concept called GAB by utilizing γδTCR as a tumor targeting domain. The γδ ECTO-alpha CD3-dimer design was found to be superior in function compared to monomers and does not induce T cell activation without simultaneous tumor engagement.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Hematology
Delphine Tardivon, Mateusz Antoszewski, Nadine Zangger, Marianne Nkosi, Jessica Sordet-Dessimoz, Rudi Hendriks, Ute Koch, Freddy Radtke
Summary: NOTCH1 gain-of-function mutations are common in B-cell chronic lymphocytic leukemia, and play a role in disease progression and chemotherapy resistance. In an in vivo mouse model of CLL, activation of Notch signaling facilitated disease initiation and promoted CLL cell proliferation and disease progression, while inhibition of Notch signaling delayed disease induction.
Article
Cell Biology
Shawn P. Fahl, Alejandra Contreras, Anjali Verma, Xiang Qiu, Christelle Harly, Freddy Radtke, Juan Carlos Zuniga-Pflucker, Cornelis Murre, Hai-Hui Xue, Jyoti Misra Sen, David L. Wiest
Summary: This study reveals a regulatory axis where T cell receptor (TCR) signaling controls TCF1 expression, which in turn regulates gamma delta T lineage commitment and effector fate. The level of TCF1 expression plays a critical role in setting the threshold for gamma delta T lineage commitment and modulating effector fate.
Article
Hematology
Mateusz Antoszewski, Nadine Fournier, Gustavo A. Ruiz Buendia, Joao Lourenco, Yuanlong Liu, Tara Sugrue, Christelle Dubey, Marianne Nkosi, Colin E. J. Pritchard, Ivo J. Huijbers, Gabriela C. Segat, Sandra Alonso-Moreno, Elisabeth Serracanta, Laura Belver, Adolfo A. Ferrando, Giovanni Ciriello, Andrew P. Weng, Ute Koch, Freddy Radtke
Summary: The high-mobility-group transcription factor Tcf1 plays an essential role in regulating chromatin accessibility and topology, allowing abnormal Notch1 signaling to convey its oncogenic function in T cell acute lymphoblastic leukemia (T-ALL). The formation of a leukemia-prone epigenetic landscape, which is dependent on Tcf1, occurs at the earliest progenitor stage before cells adopt a T lymphocyte or leukemic fate.
Article
Multidisciplinary Sciences
Gerard Llimos, Vincent Gardeux, Ute Koch, Judith F. Kribelbauer, Antonina Hafner, Daniel Alpern, Joern Pezoldt, Maria Litovchenko, Julie Russeil, Riccardo Dainese, Riccardo Moia, Abdurraouf Mokhtar Mahmoud, Davide Rossi, Gianluca Gaidano, Christoph Plass, Pavlo Lutsik, Clarissa Gerhauser, Sebastian M. Waszak, Alistair Boettiger, Freddy Radtke, Bart Deplancke
Summary: This study reveals that a non-coding variant induces transcription factor nucleation through chromatin compaction, leading to up-regulation of the AXIN2 gene and is associated with better prognosis in chronic lymphocytic leukemia.
NATURE COMMUNICATIONS
(2022)
Article
Hematology
Antonina Kurtova, Melanie Heinlein, Simon Haas, Lars Velten, Gerrit J. P. Dijkgraaf, Elaine E. Storm, Noelyn M. Kljavin, Soufiane Boumahdi, Patricia Himmels, Aurelie Herault, Andrew Mancini, Hartmut Koeppen, Monique Dail, Qingxiang Yan, Jianhuan Zhang, Ute Koch, Freddy Radtke, Zora Modrusan, Ciara Metcalfe, Robert Piskol, Frederic J. de Sauvage
Summary: The self-renewal and differentiation of stem and progenitor cells are regulated by systemic and local cues. RSPO3 is important for Wnt signaling and is usually expressed in the stem cell niche to regulate stem cell expansion and differentiation. Disrupting the niche-restricted expression of RSPO3 can affect tissue organization and lead to disorders and cancers.
Letter
Hematology
Filippo Spriano, Chiara Tarantelli, Alberto J. Arribas, Eugenio Gaudio, Luciano Cascione, Luca Aresu, Andrea Rinaldi, Emanuele Zucca, Davide Rossi, Anastasios Stathis, Maximilien Murone, Freddy Radtke, Rajwinder Lehal, Francesco Bertoni
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Medicine, Research & Experimental
Julie Terzic, Mohamed A. Abu el Maaty, Regis Lutzing, Alexandre Vincent, Rana El Bizri, Matthieu Jung, Celine Keime, Daniel Metzger
Summary: Androgen deprivation therapy is a key treatment for prostate cancer, but some cases develop into castration-resistant prostate cancer (CRPC). In this study, it was found that the major luminal cell population in CRPC is castration-resistant, with enhanced expression of inflammation and stemness markers. Additionally, hypoxia-inducible factor 1 (HIF1) signaling, which promotes malignant progression, is further activated. Inhibition of HIF1A enhances the sensitivity of Pten-deficient prostatic tumors to castration and induces apoptotic signaling in human CRPC cell lines.
EMBO MOLECULAR MEDICINE
(2023)
Article
Cell Biology
Thimios A. Mitsiadis, Pierfrancesco Pagella, Helder Gomes Rodrigues, Alexander Tsouknidas, Liza L. Ramenzoni, Freddy Radtke, Albert Mehl, Laurent Viriot
Summary: Evolutionary changes in vertebrates are often accompanied by genetic alterations that affect tooth crown shape. The Notch pathway, a highly conserved signaling pathway, plays a crucial role in morphogenetic processes, including tooth development. Experimental studies on developing mouse molars showed that the loss of the Notch-ligand Jagged1 leads to minor modifications in tooth crown shape, similar to those observed during the evolution of Muridae species. RNA sequencing analysis revealed that these alterations are caused by changes in the expression of over 2000 genes, and that Notch signaling interacts with other important morphogenetic networks, such as Wnts and Fibroblast Growth Factors. The findings from this study provide insights into the role of Notch/Jagged1-mediated signaling in dental variations during evolution.
Article
Biology
Ryosuke Sugiura, Takahiro Nakayama, Teppei Nishino, Naoto Sambe, Freddy Radtke, Masaharu Yoshihara, Satoru Takahashi
Summary: Notch1 signaling plays a crucial role in the normal development and multiple disorders of the kidney. However, the baseline signaling level in mature healthy kidneys has not been well studied. Researchers used a transgenic mouse model to label past and ongoing Notch1 signaling, and found that ongoing Notch1 activation was infrequently observed in Bowman's capsule and tubules. This suggests that Notch1 activation itself may be pathologically significant in certain disease models.
BMC RESEARCH NOTES
(2023)
Article
Hematology
Linlin Cao, Gustavo A. Ruiz Buendia, Nadine Fournier, Yuanlong Liu, Florence Armand, Romain Hamelin, Maria Pavlou, Freddy Radtke
Summary: Gain-of-function mutations in NOTCH1 are common in T-cell acute lymphoblastic leukemia (T-ALL) and targeting the Notch signaling pathway has shown promise for personalized medicine. Resistance to Notch inhibitors can occur due to mutational loss of PIK3R1, resulting in increased PI3K/AKT signaling. Combination therapy targeting CDK4/6 and NOTCH has been found to be the most effective in T-ALL xenotransplantation models.
Article
Biochemistry & Molecular Biology
Anna Y. Belorusova, Daniela Rovito, Yassmine Chebaro, Stefanie Doms, Lieve Verlinden, Annemieke Verstuyf, Daniel Metzger, Natacha Rochel, Gilles Laverny
Summary: This study demonstrates that BXL-62 and Gemini-72, two C-20-modified vitamin D analogs, restore the transcriptional activities of VDR variants unresponsive to the natural ligand. The elucidated mechanisms of action highlight the mutual adaptation between the ligand and the VDR ligand-binding pocket.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Veterinary Sciences
Masaharu Yoshihara, Teppei Nishino, Naoto Sambe, Takahiro Nayakama, Freddy Radtke, Seiya Mizuno, Satoru Takahashi
Summary: In this study, a new Gal4-dependent transgenic mouse line was generated to label protein-protein interactions in embryos. The functionality of this transgenic tool was confirmed, and it can be used to label various molecular activities in vivo.
EXPERIMENTAL ANIMALS
(2022)
Article
Medicine, Research & Experimental
Daniela Gomez Atria, Brian T. Gaudette, Jennifer Londregan, Samantha Kelly, Eric Perkey, Anneka Allman, Bhaskar Srivastava, Ute Koch, Freddy Radtke, Burkhard Ludewig, Christian W. Siebel, Russell Jh Ryan, Tanner F. Robertson, Janis K. Burkhardt, Warren S. Pear, David Allman, Ivan Maillard
Summary: In lymphopenic environments, transferred follicular B cells can transdifferentiate into marginal zone B cells, acquiring characteristics and functions similar to marginal zone B cells.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Biochemistry & Molecular Biology
Katsuya Miyajima, Chiaki Kawamoto, Satoshi Hara, Masayo Mori-Kojima, Tamae Ohye, Chiho Sumi-Ichinose, Nae Saito, Toshikuni Sasaoka, Daniel Metzger, Hiroshi Ichinose
Summary: The study revealed that dopamine (DA) supply in peripheral organs originates from sympathetic neurons, with decreased TH protein and NA levels leading to a decrease in DA content in the heart and pancreas. TH-immunoreactive cells were found in the stomach and lung, showing a decreasing trend in TH protein levels but not in DA levels. Additionally, there was a significant correlation between DA content in the kidney and plasma DOPA concentration.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Oncology
Lydia Meder, Alexandra Florin, Luka Ozretic, Marieke Nill, Mirjam Koker, Sonja Meemboor, Freddy Radtke, Linda Diehl, Roland T. Ullrich, Margarete Odenthal, Reinhard Buettner, Lukas C. Heukamp
Summary: This study showed that Notch1 deficiency contributes to the development of lung adenocarcinomas by increasing TAZ expression in a subgroup of patients with mutated Kras driven lung tumors. The findings suggest potential benefits of TAZ signaling blockade in these patients.
PATHOLOGY & ONCOLOGY RESEARCH
(2021)
