Article
Immunology
Jack Firth, Jingjing Sun, Vaques George, Jian-Dong Huang, Mona Bajaj-Elliott, Kenth Gustafsson
Summary: This study found that bacterial outer-membrane vesicles (OMVs) can activate gamma delta T cells, which have anti-tumor capabilities. The OMVs induced a broad inflammatory response and stimulated the expansion of V gamma 9V delta 2 T cells. These activated T cells exhibited cytolytic activity against breast and leukemia cell lines.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Jiaqing Zhou, Jingjing Zhang, Lu Tao, Kexin Peng, Qiaoan Zhang, Kexiang Yan, Jing Luan, Jiewen Pan, Xiaohui Su, Jiping Sun, Zhenghua Zhang, Lei Shen
Summary: In this study, the authors investigated the role of V gamma 9V delta 2 T cells in the development and progression of psoriasis vulgaris (PV). They found that PV patients had decreased circulating V gamma 9V delta 2 T cells but enhanced proliferation and increased production of IFN-gamma and TNF-alpha by these cells. The authors also discovered that the phosphoantigen sensor butyrophilin 3A1 (BTN3A1) was expressed at higher levels on monocytes from PV patients and blocking BTN3A1 suppressed V gamma 9V delta 2 T cell activation. They further observed that CD14(+) cells in PV skin lesions highly expressed BTN3A1. These findings suggest a crucial regulatory role of BTN3A1 on monocytes in V gamma 9V delta 2 T cell activation and highlight BTN3A1 as a potential therapeutic target for psoriasis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
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
Immunology
Chloe Laplagne, Laetitia Ligat, Juliet Foote, Frederic Lopez, Jean-Jacques Fournie, Camille Laurent, Salvatore Valitutti, Mary Poupot
Summary: This study demonstrates that V gamma 9V delta 2 T cells can self-activate through exogenous PAgs independently, involving the molecules TCR, BTN3A1, and BTN2A1. Additionally, the involvement of ABCA-1 in the transfer of exogenous PAgs inside V gamma 9V delta 2 T cells was proposed, indicating a potential new mechanism for activation of these cytotoxic T cells against tumor cells.
CELLULAR & MOLECULAR IMMUNOLOGY
(2021)
Article
Cell & Tissue Engineering
Gitte Holmen Olofsson, Sara Ram Pedersen, Pia Aehnlich, Inge Marie Svane, Manja Idorn, Per Thor Straten
Summary: Human V gamma 9V delta 2 T cells are a unique type of T cells with both antigen-presenting and cytotoxic properties. A small fraction of these cells, CD4(+) V gamma 9V delta 2 T cells, can be expanded in vitro and are potent in killing cancer cells, especially when co-expressing CD56.
Article
Immunology
Laetitia Gay, Soraya Mezouar, Carla Cano, Etienne Foucher, Melanie Gabriac, Marie Fullana, Loui Madakamutil, Jean-Louis Mege, Daniel Olive
Summary: This study reveals the crucial role of V gamma 9V delta 2 T cells in the immune response against C. burnetii infection. BTN3A and BTN2A are required for the activation of V gamma 9V delta 2 T cells. C. burnetii infection induces increased expression of BTN3A and BTN2A, leading to the activation of V gamma 9V delta 2 T cells. An activating antibody for BTN3A enhances the antimicrobial functions of V gamma 9V delta 2 T cells against C. burnetii.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Medicine, Research & Experimental
Yi Wang, Nan Ji, Yang Zhang, Junsheng Chu, Changcun Pan, Peng Zhang, Weiwei Ma, Xueguang Zhang, Jianzhong Jeff Xi, Mingze Chen, Yonghui Zhang, Liwei Zhang, Tao Sun
Summary: The study investigates the therapeutic potential of human V gamma 9V delta 2 T cells in glioblastoma (GBM) treatment. The results show that V gamma 9V delta 2 T cells have a robust anti-tumor effect in some glioma cases, while weaker in others. Elevated expression of BTN2A1 and BTN3A1 correlates with improved response. Weak anti-tumor effect tumors can be sensitized using a BTN3A1 agonistic antibody or bisphosphonates. Genetically engineered V gamma 9V delta 2 T cells, i.e., Car-B7H3, demonstrate promising efficacy. These findings highlight the versatility of V gamma 9V delta 2 T cells for GBM treatment.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Mako Tomogane, Yusuke Sano, Daiki Shimizu, Teruki Shimizu, Masatsugu Miyashita, Yuki Toda, Shigekuni Hosogi, Yoshimasa Tanaka, Shinya Kimura, Eishi Ashihara
Summary: The study found that PD-1 blockade did not enhance the cytotoxicity of gamma delta T cells against PD-L1(high) cancer cells, but the anti-PD-L1 monoclonal antibody showed an increase in cytotoxicity. PD-L1 knockdown did not affect gamma delta T cell cytotoxicity. The findings suggest that anti-PD-L1 mAb treatment can enhance the cytotoxicity of gamma delta T cells against PD-L1(high) cancer cells.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Immunology
Anna Bold, Heike Gross, Elisabeth Holzmann, Stefan Knop, Timm Hoeres, Martin Wilhelm
Summary: γδ T cells are suitable candidates for cellular immunotherapy in cancer due to their properties of both the innate and acquired immune systems. However, many current stimulation protocols conflict with the basic principles of Good Manufacturing Practice (GMP) by using xenogenic materials and potentially hazardous supplements.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Mako Tomogane, Maho Omura, Yusuke Sano, Daiki Shimizu, Yuki Toda, Shigekuni Hosogi, Shinya Kimura, Eishi Ashihara
Summary: The study shows that amplification of gamma delta T cells requires CD14(+) monocytes as accessory cells, and the surface expression of BTN3A1 on monocytes positively correlates with the expansion of gamma delta T cells. Additionally, treatment with BTN3A1-Fc can enhance the expansion efficiency of gamma delta T cells with poor expansion capacity.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Immunology
Chirine Rafia, Clement Loizeau, Ophelie Renoult, Christelle Harly, Claire Pecqueur, Noemie Joalland, Emmanuel Scotet
Summary: The eradication of cancer remains a clinical challenge, and additional therapeutic strategies like immunotherapies need to be explored. It has been found that TGF-beta interferes with the antigenic activation of human V gamma 9V delta 2 T cells, impairing their cytolytic activity. These observations provide insights for understanding and targeting the impact of tumor microenvironment components on the antitumor activity of human T cell effectors.
FRONTIERS IN IMMUNOLOGY
(2023)
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
Oncology
Xin Huang, Cunchuan Wang, Ningxia Wang
Summary: The study found that introducing V gamma 9V delta 2 T cells can synergistically enhance the inhibitory activity of CDDP against breast cancer cells, producing more pronounced effects at the cellular level.
CANCER CELL INTERNATIONAL
(2021)
Article
Biochemistry & Molecular Biology
Yizheng Wang, Linan Wang, Naohiro Seo, Satoshi Okumura, Tae Hayashi, Yasushi Akahori, Hiroshi Fujiwara, Yasunori Amaishi, Sachiko Okamoto, Junichi Mineno, Yoshimasa Tanaka, Takuma Kato, Hiroshi Shiku
Summary: The benefits of CAR-T therapy for solid tumors have been limited so far due to disappointing clinical trial results and the time and cost intensive preparation of CAR-T cell products. However, using third-party donor derived CAR-T cell products could potentially overcome these challenges. Vγ9Vδ2 T cells, which have potent antitumor activity, could be a potential source of 'off-the-shelf' CAR-T cell products for successful allogeneic adoptive immunotherapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Lihua Deng, Anna Harms, Sarina Ravens, Immo Prinz, Likai Tan
Summary: The heterogeneity of V delta 2(+) TCRs is primarily determined by TRDJ-usage and the length of CDR3aa sequences. Public V delta 2(+) TCRs result from germline-like rearrangement and synonymous codons, and they are associated with a higher expansion status.
FRONTIERS IN IMMUNOLOGY
(2022)
Editorial Material
Immunology
Christelle Harly, Avinash Bhandoola
JOURNAL OF EXPERIMENTAL MEDICINE
(2020)
Article
Oncology
Lucine Marotte, Sylvain Simon, Virginie Vignard, Emilie Dupre, Malika Gantier, Jonathan Cruard, Jean-Baptiste Alberge, Melanie Hussong, Cecile Deleine, Jean-Marie Heslan, Jonathan Shaffer, Tiffany Beauvais, Joelle Gaschet, Emmanuel Scotet, Delphine Fradin, Anne Jarry, Tuan Nguyen, Nathalie Labarriere
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2020)
Article
Immunology
Jeanne Perroteau, Benjamin Navet, Marie-Claire Devilder, Leslie Hesnard, Emmanuel Scotet, Laurent Gapin, Xavier Saulquin, Laetitia Gautreau-Rolland
EUROPEAN JOURNAL OF IMMUNOLOGY
(2020)
Article
Immunology
Christelle Harly, Devin Kenney, Yueqiang Wang, Yi Ding, Yongge Zhao, Parirokh Awasthi, Avinash Bhandoola
FRONTIERS IN IMMUNOLOGY
(2020)
Review
Immunology
Noemie Joalland, Emmanuel Scotet
FRONTIERS IN IMMUNOLOGY
(2020)
Article
Medicine, Research & Experimental
Anna Vyborova, Dennis X. Beringer, Domenico Fasci, Froso Karaiskaki, Eline van Diest, Lovro Kramer, Aram de Haas, Jasper Sanders, Anke Janssen, Trudy Straetemans, Daniel Olive, Jeanette Leusen, Lola Boutin, Steven Nedellec, Samantha L. Schwartz, Michael J. Wester, Keith A. Lidke, Emmanuel Scotet, Diane S. Lidke, Albert Heck, Zsolt Sebestyen, Jurgen Kuball
JOURNAL OF CLINICAL INVESTIGATION
(2020)
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
Oncology
Marisa Capitao, Justine Perrin, Sylvain Simon, Sebastien Gouard, Nicolas Chouin, Frank Bruchertseifer, Alfred Morgenstern, Latifa Rbah-Vidal, Michel Cherel, Emmanuel Scotet, Nathalie Labarriere, Yannick Guilloux, Joelle Gaschet
Summary: The study demonstrates that targeting PD-L1 with bismuth-213, an alpha-particle emitter, leads to efficient anti-tumor response, significant tumor growth delay, and improved survival in human melanoma, suggesting that anti-PD-L1 antibodies could be a promising therapeutic option for targeted alpha-particle therapy.
Article
Immunology
Christelle Harly, Stephen Paul Joyce, Charlotte Domblides, Thomas Bachelet, Vincent Pitard, Charlotte Mannat, Angela Pappalardo, Lionel Couzi, Sonia Netzer, Layal Massara, Emilie Obre, Omar Hawchar, Lydia Lartigue, Stephane Claverol, Carla Cano, Jean-Francois Moreau, Isabelle Mahouche, Isabelle Soubeyran, Rodrigue Rossignol, Benoit Viollet, Carrie R. Willcox, Fiyaz Mohammed, Benjamin E. Willcox, Benjamin Faustin, Julie Dechanet-Merville
Summary: In this study, the researchers identified EphA2 as a stress antigen recognized by human Vγ9Vδ1 TCR, with EphA2 being coordinately recognized by ephrin A to activate γδ TCR. The expression of EphA2 was found to be up-regulated in cancer cells undergoing AMPK-dependent metabolic reprogramming, and coexpression of EphA2 and active AMPK in tumors was associated with increased CD3 T cell infiltration in human colorectal cancer tissues.
SCIENCE IMMUNOLOGY
(2021)
Article
Immunology
Gang Ren, Binbin Lai, Christelle Harly, Songjoon Baek, Yi Ding, Mingzhu Zheng, Yaqiang Cao, Kairong Cui, Yu Yang, Jinfang Zhu, Gordon L. Hager, Avinash Bhandoola, Keji Zhao
Summary: The differentiation of innate lymphoid cells (ILCs) from hematopoietic stem cells requires the progression through several multipotent progenitor stages. This study shows that there are distinct accessible chromatin regions in all lymphoid progenitors (ALPs), early ILC precursors (EILPs), and ILC precursors (ILCPs). Single-cell MNase-seq analyses reveal that EILPs contain subpopulations epigenetically primed toward dendritic cell or ILC lineages. Key transcription factors TCF-1 and GATA3 are found to be indispensable for the epigenetic priming of lineage-defining sites for ILCs at the EILP stage.
Article
Biochemistry & Molecular Biology
Yongbing Zhao, Supriya V. Vartak, Andrea Conte, Xiang Wang, David A. Garcia, Evan Stevens, Seol Kyoung Jung, Kyong-Rim Kieffer-Kwon, Laura Vian, Timothy Stodola, Francisco Moris, Laura Chopp, Silvia Preite, Pamela L. Schwartzberg, Joseph M. Kulinski, Ana Olivera, Christelle Harly, Avinash Bhandoola, Elisabeth F. Heuston, David M. Bodine, Raul Urrutia, Arpita Upadhyaya, Matthew T. Weirauch, Gordon Hager, Rafael Casellas
Summary: This study analyzes 500 mouse and human primary cells and reveals two groups of co-localized transcription factors, one involved in tissue-specific transcription and the other functioning universally in all tissues. The study also uncovers how the universal stripe factors enhance accessibility and residence time of co-localized partners.
Article
Immunology
Christelle Harly, Jacques Robert, Francois Legoux, Olivier Lantz
Summary: Innate-like T cells display characteristics of both ILCs and mainstream alpha beta T cells, and are probably present in all vertebrates. Their main characteristics are better known in amphibians and mammals. These cells include both gamma delta and alpha beta T cells, and each subset fulfills nonredundant roles related to their Ag specificity.
JOURNAL OF IMMUNOLOGY
(2022)