Article
Cell Biology
Mariana V. Rosemblatt, Brian Parra-Tello, Pedro Briceno, Elizabeth Rivas-Yanez, Suat Tucer, Juan Saavedra-Almarza, Pilar Hormann, Brandon A. Martinez, Alvaro Lladser, Mario Rosemblatt, Caglar Cekic, Maria Rosa Bono, Daniela Sauma
Summary: This study assessed the impact of CD73 deficiency on CD8+ T cells and found that CD73 has a dual effect, favoring homeostatic survival but reducing survival under antigenic stimulation. Special attention should be given to these aspects when considering CD73 blockade in the design of novel antitumor therapies.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Cell Biology
Pedro Briceno, Elizabeth Rivas-Yanez, Mariana V. Rosemblatt, Brian Parra-Tello, Paula Farias, Leonardo Vargas, Valeska Simon, Cesar Cardenas, Alvaro Lladser, Flavio Salazar-Onfray, Alvaro A. Elorza, Mario Rosemblatt, Maria Rosa Bono, Daniela Sauma
Summary: During CD8+ T cell differentiation, CD73 and adenosine may have an autocrine effect on cytotoxic T cells' metabolic fitness, influencing their functional properties.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Developmental Biology
Annika Missel, Lena Walenta, Katja Eubler, Nadine Mundt, Hanna Heikela, Ulrich Pickl, Matthias Trottmann, Bastian Popper, Matti Poutanen, Leena Strauss, Frank-Michael Koehn, Lars Kunz, Marc Spehr, Artur Mayerhofer
Summary: Extracellular ATP has been found to play a role in cytokine production in human testicular cells, with adenosine possibly involved as a metabolite. Pharmacological inhibition of ENTPD1 reduced pro-inflammatory cytokines, suggesting a link to ATP metabolites like adenosine. Targeting ATP metabolites or adenosine receptors could potentially reduce inflammatory events in the testis, offering novel therapeutic avenues for male infertility treatment.
MOLECULAR HUMAN REPRODUCTION
(2021)
Article
Cell Biology
Rolando A. Cuevas, Ryan Wong, Pouya Joolharzadeh, William J. Moorhead III, Claire C. Chu, Jack Callahan, Alex Crane, Camille K. Boufford, Angelina M. Parise, Aneesha Parwal, Parya Behzadi, Cynthia St. Hilaire
Summary: Arterial calcification due to deficiency of CD73 (ACDC) is a rare genetic disease caused by a loss-of-function mutation in the NT5E gene encoding the ecto-5'-nucleotidase (cluster of differentiation 73, CD73) enzyme. Patients with ACDC develop vessel arteriomegaly, tortuosity, and vascular calcification in their lower extremity arteries. Our study investigates whether CD73-derived adenosine modifies TGF beta signaling in vascular smooth muscle cells (SMCs) and identifies a novel link between adenosine and TGF beta signaling, where adenosine signaling via the A2b adenosine receptor attenuates TGF beta signal-ing to regulate SMC homeostasis.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2023)
Article
Oncology
Emily Maria Ploeg, Douwe Freerk Samplonius, Xiao Xiong, Xiurong Ke, Mark Alexander Johannes Martinus Hendriks, Isabel Britsch, Anne Paulien van Wijngaarden, Hao Zhang, Wijnand Helfrich
Summary: CD73 is an enzyme that converts pro-inflammatory extracellular ATP from stressed cancer cells to anti-inflammatory adenosine. CD73 antagonistic antibodies are used to suppress immune checkpoints, but they may also affect normal cells. Therefore, a more selective approach is needed to inhibit CD73 specifically in cancer cells.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Review
Immunology
Zoya Kurago, Gang Guo, Huidong Shi, Roni J. Bollag, Michael W. Groves, J. Kenneth Byrd, Yan Cui
Summary: CD73 is a crucial immune checkpoint that produces adenosine and plays a role in tumor development and therapy. Inhibition of CD73-adenosinergic pathway improves antitumor immunity and is being tested in clinical trials.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Integrative & Complementary Medicine
Yuanbing Zhu, Zhiqi Zhuang, Qiaofeng Wu, Sirui Lin, Na Zhao, Qun Zhang, Lushuang Xie, Shuguang Yu
Summary: This study found that moxibustion can improve ulcerative colitis by regulating the expression of immune cells and adenosine receptors, affecting the ATP purine signal metabolism pathway, and alleviating gut inflammation in mice.
AMERICAN JOURNAL OF CHINESE MEDICINE
(2021)
Review
Immunology
Meihong Da, Luxia Chen, Alexander Enk, Sabine Ring, Karsten Mahnke
Summary: Adenosine (Ado) has immunosuppressive effects, and the ectoenzyme CD73 is crucial for the production of extracellular Ado. CD73 is highly expressed in regulatory T cells (Tregs) and upregulated after activation. Ado generated by CD73(+) Tregs plays a role in immune suppression of dendritic cells, monocytes, and T cells, making CD73 a novel checkpoint inhibitor in immunosuppressive environments such as tumors. Therapeutic intervention targeting CD73 is currently under investigation.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Lydia Meziani, Marine Gerbe de Thore, Celine Clemenson, Winchygn Liu, Pierre-Antoine Laurent, Michele Mondini, Marie-Catherine Vozenin, Eric Deutsch
Summary: CD73 targeting can improve the antitumor effects of irradiation and immune checkpoint inhibitor treatment, and the dosing regimen and iCOS expression are important factors that affect the therapeutic efficacy.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Review
Biochemistry & Molecular Biology
Chenglai Xia, Shuanghong Yin, Kenneth K. W. To, Liwu Fu
Summary: Cancer development is influenced by an immunosuppressive tumor microenvironment that weakens the immune response and allows tumors to evade detection. The enzymes CD39 and CD73 convert ATP into adenosine, which interacts with adenosine receptors to regulate immune function. Specifically, the A2AR receptor suppresses the immune system through cAMP signaling. CD39, CD73, and A2AR are potential therapeutic targets for enhancing antitumor immunity. Clinical trials are underway to investigate monoclonal antibodies and small molecule inhibitors that target the CD39/CD73/A2AR pathway, either alone or in combination with anti-PD-1/PD-L1 therapies.
Article
Oncology
Cheryl M. Cameron, Brian Richardson, Jackelyn B. Golden, Yee Peng Phoon, Banumathi Tamilselvan, Lukas Pfannenstiel, Samjhana Thapaliya, Gustavo Roversi, Xing-Huang Gao, Leah L. Zagore, Mark J. Cameron, Brian R. Gastman
Summary: This study identifies novel dysregulated pathways in CD8 T cells within the tumor microenvironment, including bile acid and peroxisome pathway-related metabolism and mammalian target of rapamycin signaling pathways. These findings have important implications for the improvement of therapeutic approaches in melanoma.
FRONTIERS IN ONCOLOGY
(2023)
Article
Multidisciplinary Sciences
Remi Samain, Oscar Maiques, Joanne Monger, Hoyin Lam, Juliana Candido, Samantha George, Nicola Ferrari, Leonie Kohihammer, Sophia Lunetto, Adrian Varela, Jose L. Orgaz, Felip Vilardell, Jorge Juan Olsina, Xavier Matias-Guiu, Debashis Sarker, Adrian Biddle, Frances R. Balkwill, Jim Eyles, Robert W. Wilkinson, Hemant M. Kocher, Fernando Calvo, Claire M. Wells, Victoria Sanz-Moreno
Summary: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis due to its high metastasis tendency and immunosuppressive microenvironment. The ROCK-Myosin II activity in PDAC cells supports an amoeboid invasive and immunosuppressive program, leading to in vivo metastasis. CD73, an immune checkpoint, is highly expressed in amoeboid PDAC cells and contributes to their invasive, metastatic, and immunomodulatory traits.
Article
Cell Biology
Hannah S. Sperber, Kyle A. Raymond, Mohamed S. Bouzidi, Tongcui Ma, Silvana Valdebenito, Eliseo A. Eugenin, Nadia R. Roan, Steven G. Deeks, Sandra Winning, Joachim Fandrey, Roland Schwarzer, Satish K. Pillai
Summary: Understanding the molecular characteristics of latently infected cells is crucial for curing HIV infection. This study identifies CD73 as a key surface marker of latent cells and reveals the association between adenosine signaling and viral quiescence. The findings highlight the need for developing HIV-cure strategies targeting this axis.
Article
Biology
Ivan Maslov, Oleksandr Volkov, Polina Khorn, Philipp Orekhov, Anastasiia Gusach, Pavel Kuzmichev, Andrey Gerasimov, Aleksandra Luginina, Quinten Coucke, Andrey Bogorodskiy, Valentin Gordeliy, Simon Wanninger, Anders Barth, Alexey Mishin, Johan Hofkens, Vadim Cherezov, Thomas Gensch, Jelle Hendrix, Valentin Borshchevskiy
Summary: Single-molecule FRET experiments with human A2A adenosine receptor in lipid nanodiscs reveal its conformational dynamics and activation. This study establishes a general smFRET platform for GPCR investigations, which has potential applications in drug screening and mechanism-of-action studies.
COMMUNICATIONS BIOLOGY
(2023)
Article
Medicine, Research & Experimental
Qiu-Yang Jin, Ying-Shuang Li, Xing-Hui Qiao, Jia-Wei Yang, Xiu-Li Guo
Summary: Tumor immunotherapy has emerged as an innovative and advantageous treatment method, but still requires assistance for clinical application due to its complexity. Galectins modulated in the tumor microenvironment can regulate immune system disorders to resist tumor growth, suggesting that combination therapy of targeted anti-galectins with immunotherapy may be promising for tumor treatment. This review discusses the expression and immune functions of different galectins in tumor microenvironment, highlighting the potential value of anti-galectins in combination with checkpoint inhibitors for tumor immunotherapy.
Article
Oncology
Adi Sharbi-Yunger, Mareike Grees, Gal Cafri, David Bassan, Stefan B. Eichmuller, Esther Tzehoval, Jochen Utikal, Viktor Umansky, Lea Eisenbach
INTERNATIONAL JOURNAL OF CANCER
(2019)
Article
Oncology
Dominik S. Gangkofner, Dana Holzinger, Lea Schroeder, Stefan B. Eichmueller, Inka Zoernig, Dirk Jaeger, Gunnar Wichmann, Andreas Dietz, Martina A. Broglie, Christel Herold-Mende, Gerhard Dyckhoff, Paolo Boscolo-Rizzo, Jasmin Ezic, Ralf B. Marienfeld, Peter Moeller, Gunnar Voelkel, Johann M. Kraus, Hans A. Kestler, Cornelia Brunner, Patrick J. Schuler, Marlene Wigand, Marie N. Theodoraki, Johannes Doescher, Thomas K. Hoffmann, Michael Pawlita, Julia Butt, Tim Waterboer, Simon Laban
INTERNATIONAL JOURNAL OF CANCER
(2019)
Article
Virology
Elena Busch, Kristina D. Kubon, Johanna K. M. Mayer, Gemma Pidelaserra-Marti, Jessica Albert, Birgit Hoyler, Johannes P. W. Heidbuechel, Kyle B. Stephenson, Brian D. Lichty, Wolfram Osen, Stefan B. Eichmueller, Dirk Jaeger, Guy Ungerechts, Christine E. Engeland
Article
Multidisciplinary Sciences
Philipp Schroeter, Laura Hartmann, Wolfram Osen, Daniel Baumann, Rienk Offringa, David Eisel, Juergen Debus, Stefan B. Eichmueller, Stefan Rieken
SCIENTIFIC REPORTS
(2020)
Article
Biochemical Research Methods
Franziska Hoerhold, David Eisel, Marcus Oswald, Amol Kolte, Daniela Roell, Wolfram Osen, Stefan B. Eichmueller, Rainer Koenig
PLOS COMPUTATIONAL BIOLOGY
(2020)
Article
Oncology
Tao Ran, Stefan B. Eichmueller, Patrick Schmidt, Michael Schlander
INTERNATIONAL JOURNAL OF CANCER
(2020)
Letter
Oncology
Tao Ran, Stefan B. Eichmueller, Patrick Schmidt, Michael Schlander
INTERNATIONAL JOURNAL OF CANCER
(2021)
Article
Multidisciplinary Sciences
Laura Hartmann, Philipp Schroeter, Wolfram Osen, Daniel Baumann, Rienk Offringa, Mahmoud Moustafa, Rainer Will, Juergen Debus, Stephan Brons, Stefan Rieken, Stefan B. Eichmueller
SCIENTIFIC REPORTS
(2020)
Article
Oncology
Michael Kilian, Mirco Friedrich, Khwab Sanghvi, Edward Green, Stefan Pusch, Daisuke Kawauchi, Martin Loewer, Jana K. Sonner, Christopher Kraemer, Julia Zaman, Stefanie Jung, Michael O. Breckwoldt, Gerald Willimksy, Stefan B. Eichmueller, Andreas von Deimling, Wolfgang Wick, Felix Sahm, Michael Platten, Lukas Bunse
Summary: In this study, glioma-specific immunogenic neoepitopes were identified using peptide-based ELISpot assays and droplet-based single-cell TCR sequencing in MHC-humanized mice. The efficacy of TCR-transgenic T-cell therapy against gliomas was demonstrated in a humanized orthotopic glioma model.
CLINICAL CANCER RESEARCH
(2022)
Article
Cell & Tissue Engineering
Pablo Hernandez-Malmierca, Dominik Vonficht, Alexandra Schnell, Hannah J. Uckelmann, Alina Bollhagen, Mohamed A. A. Mahmoud, Sophie-Luise Landua, Elise van der Salm, Christine L. Trautmann, Simon Raffel, Florian Gruenschlaeger, Raphael Lutz, Michael Ghosh, Simon Renders, Nadia Correia, Elisa Donato, Karin O. Dixon, Christoph Hirche, Carolin Andresen, Claudia Robens, Paula S. Werner, Tobias Boch, David Eisel, Wolfram Osen, Franziska Pilz, Adriana Przybylla, Corinna Klein, Frank Buchholz, Michael D. Milsom, Marieke A. G. Essers, Stefan B. Eichmueller, Wolf-Karsten Hofmann, Daniel Nowak, Daniel Huebschmann, Michael Hundemer, Christian Thiede, Lars Bullinger, Carsten Mueller-Tidow, Scott A. Armstrong, Andreas Trumpp, Vijay K. Kuchroo, Simon Haas
Summary: Hematopoietic stem and progenitor cells (HSPCs) can effectively eliminate malignant cells through bidirectional interactions with CD4(+) T cells, thereby preventing the onset of hematological cancers.
Article
Cell Biology
Tsu-Yang Chao, Theresa Kordass, Wolfram Osen, Stefan B. Eichmueller
Summary: The miRNAs miR-134-3p and miR-224-3p were found to directly interact with the SOX9 gene and inhibit its expression in breast cancer cells. These two miRNAs were down-regulated in breast cancer tissues, suggesting their potential role as tumor suppressors in breast cancer progression.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2023)
Article
Oncology
Niklas Kehl, Michael Kilian, Julius Michel, Tim R. Wagner, Sebastian Uhrig, Alexander Brobeil, Lilli-Sophie Sester, Sven Blobner, Simon Steiger, Michael Hundemer, Niels Weinhold, Karsten Rippe, Stefan Froehling, Stefan B. Eichmueller, Lukas Bunse, Carsten Mueller-Tidow, Hartmut Goldschmidt, Michael Platten, Marc-Steffen Raab, Mirco J. Friedrich
Summary: Multiple myeloma (MM) is a rare and aggressive hematological malignancy, and its classification and evolution can be deciphered by molecular features. IgE type MM is a subtype with a small percentage but poor prognosis, and currently there is limited genetic and immunological data available. In this study, comprehensive analysis at the genomic and immune repertoire level revealed the pathophysiological mechanisms and potential targeted therapy opportunities for IgE type MM.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Oncology
Laura Hartmann, Wolfram Osen, Oliver L. Eichmueller, Theresa Kordass, Jennifer Furkel, Elke Dickes, Carissa Reid, Jurgen Debus, Stephan Brons, Amir Abdollahi, Mahmoud Moustafa, Stefan Rieken, Stefan B. Eichmueller
Summary: Radiotherapy can activate tumor-specific immune responses in patients and combining carbon ion radiotherapy with immune checkpoint inhibition can reshape the immune cell composition in tumors and induce complete rejection of both irradiated and non-irradiated tumors.
Article
Oncology
Antonino A. A. Pane, Theresa Kordass, Agnes Hotz-Wagenblatt, Elke Dickes, Annette Kopp-Schneider, Rainer Will, Barbara Seliger, Wolfram Osen, Stefan B. B. Eichmueller
Summary: This study identified several miRNA species that can affect the susceptibility of melanoma cells to T cell-mediated killing. These miRNAs may represent attractive candidates for novel therapy approaches against melanoma and other tumors.
CLINICAL AND TRANSLATIONAL MEDICINE
(2023)
Article
Immunology
David Eisel, Krishna Das, Elke Dickes, Rainer Koenig, Wolfram Osen, Stefan B. Eichmueller
FRONTIERS IN IMMUNOLOGY
(2019)