Review
Immunology
Ines Sophie Schaedlich, Riekje Winzer, Joschi Stabernack, Eva Tolosa, Tim Magnus, Bjoern Rissiek
Summary: In ischemic stroke, disruption of energy supply leads to primary neuronal injury and secondary sterile inflammation. ATP released during brain ischemia triggers an inflammatory cascade by activating microglia and recruiting immune cells, while the CD39 and CD73 enzymes degrade ATP into adenosine to balance the inflammatory environment. Adenosine has neuroprotective effects through A(1) receptor-mediated inhibition of excitotoxicity and anti-inflammatory capacities via A(2A) receptor activation.
SEMINARS IN IMMUNOPATHOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Ling Liang, Lei-Lei Yang, Wenjie Wang, Cailing Ji, Lei Zhang, Yiyi Jia, Yuxia Chen, Xueqiang Wang, Jie Tan, Zhi-Jun Sun, Quan Yuan, Weihong Tan
Summary: The long-term accumulation of adenosine (Ado) in tumor tissues contributes to the establishment of an immunosuppressive tumor microenvironment and the promotion of tumor development. Regulation of Ado metabolism, particularly through the activity of adenosine kinase (ADK), is essential for blocking Ado-mediated immunosuppression. Calcium phosphate-reinforced iron-based metal-organic frameworks (CaP@Fe-MOFs) are designed to reduce Ado accumulation in the tumor microenvironment and inhibit Ado-mediated immunosuppressive responses by promoting ADK-mediated phosphorylation and relieving the hypoxic tumor microenvironment.
ADVANCED MATERIALS
(2021)
Article
Oncology
Yu Bai, Xin Zhang, Jie Zheng, Ziyi Liu, Zhenfan Yang, Xiaolin Zhang
Summary: This study reports a novel A2aR antagonist, DZD2269, which can reverse the immunosuppressive effects mediated by A2aR in the tumor microenvironment. In vitro and mouse model experiments showed that DZD2269 inhibits immunosuppression induced by high adenosine levels and exhibits enhanced anti-tumor effects when combined with immune checkpoint inhibitors, radiotherapy, or chemotherapy. The phase 1 clinical study also confirmed the pharmacological effects of DZD2269.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Juergen Schrader
Summary: This article reviews Geoffrey Burnstock's personal achievements and his contributions to extracellular purine metabolism. The article also provides an overview of current research in this field and addresses some unresolved issues.
PURINERGIC SIGNALLING
(2022)
Review
Immunology
Luxia Chen, Mohamad Alabdullah, Karsten Mahnke
Summary: Adenosine is an immunosuppressive agent produced during inflammation, which can promote tissue healing. However, in chronic inflammation, the anti-inflammatory actions of adenosine may sustain the inflammation and prevent tissue clearance, leading to an increased risk of tumor formation.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Immunology
Changfa Sun, Bochu Wang, Shilei Hao
Summary: The adenosine-A2AR pathway plays a crucial role in regulating immune responses and tumor progression. Blocking this pathway can inhibit tumor growth and has potential synergistic effects with CAR T cell therapy.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Giulia Monticone, Zhi Huang, Fred Csibi, Silvana Leit, David Ciccone, Ameya S. Champhekar, Jermaine E. Austin, Deniz A. Ucar, Fokhrul Hossain, Salome V. Ibba, A. Hamid Boulares, Nicholas Carpino, Keli Xu, Samarpan Majumder, Barbara A. Osborne, Christine Loh, Lucio Miele
Summary: This study reveals a novel immunosuppressive pathway by regulating the Cbl-b and Notch1 signaling pathways to enhance the effector functions of CD8+ T cells, thus improving anti-cancer responses and reducing sensitivity to immunosuppression.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Borja Ruiz-Fernandez de Cordoba, Haritz Moreno, Karmele Valencia, Naiara Perurena, Pablo Ruedas, Thomas Walle, Alberto Pezonaga-Torres, Juan Hinojosa, Elisabet Guruceaga, Antonio Pineda-Lucena, Marta Abengozar-Muela, Denis Cochonneau, Carolina Zandueta, Susana Martinez-Canarias, Alvaro Teijeira, Daniel Ajona, Sergio Ortiz-Espinosa, Xabier Morales, Carlos Ortiz de Solorzano, Marta Santisteban, Luis Ramos-Garcia, Laura Guembe, Vratislav Strnad, Dominique Heymann, Sandra Hervas-Stubbs, Ruben Pio, Maria E. Rodriguez-Ruiz, Carlos E. de Andrea, Silvestre Vicent, Ignacio Melero, Fernando Lecanda, Rafael Martinez-Monge
Summary: Locoregional failure in breast cancer patients after surgery and irradiation is linked to a poor prognosis. The ENPP1/HP axis is exploited by tumor cells to promote local recurrence by suppressing immune cells. Blocking this axis offers new opportunities for therapeutic intervention.
Review
Pharmacology & Pharmacy
Tejinder Kaur, Brenna Weadick, Thomas A. Mace, Kajal Desai, Hannah Odom, Rajgopal Govindarajan
Summary: Adenosine compartmentalization plays a significant role in suppressing immune cell function in the tumor microenvironment. Nucleoside transporters, responsible for the localization and translocation of adenosine, are crucial for adenosine disposition. Targeting nucleoside transporters could potentially attenuate the accumulation of immunosuppressive adenosine in solid tumors.
PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Health Care Sciences & Services
Magis Mandapathil, Miroslaw J. Szczepanski, Edwin K. Jackson, Stephan Lang, Theresa L. Whiteside
Summary: The study suggests that breast cancer cells producing ADO are conducive to the induction of Tr1 cells, which exhibit higher immunosuppressive activity. Inhibiting ectonucleotidases and A2A receptors can reduce the proliferative suppression mediated by Tr1 cells.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Article
Immunology
Nicolly Espindola Gelsleichter, Juliana Hofstatter Azambuja, Dominique Santos Rubenich, Elizandra Braganhol
Summary: Glioblastoma (GB), the most aggressive brain tumor, shows heterogeneity, strong invasive ability, and high resistance to therapy due to immunosuppressive mechanisms. CD73, an overexpressed enzyme in GB, acts through adhesion protein activity or AMP catalysis to adenosine (ADO) generation, inducing changes in tumor cells and tumor microenvironment cells (TME). CD73 is considered a potential target for GB therapy. This review explores the roles of CD73 and ADO receptors in GB, their impact on immune interactions, therapeutic strategies, and the necessary steps to move this approach from preclinical to clinical use.
IMMUNOLOGY LETTERS
(2023)
Review
Oncology
Thamiris Becker Scheffel, Nathalia Grave, Pedro Vargas, Fernando Mendonca Diz, Liliana Rockenbach, Fernanda Bueno Morrone
Summary: Glioblastoma is a highly malignant subtype of glioma, and the immune landscape within the tumor microenvironment plays a crucial role in influencing therapy outcomes. The presence of multiple immunosuppression pathways, particularly the adenosine pathway, poses significant obstacles to immune-based cancer therapies and can contribute to treatment resistance. Research focusing on immune checkpoints and the adenosine pathway may provide insights into potential targets for improving tumor treatment strategies.
FRONTIERS IN ONCOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Massimiliano Gasparrini, Leonardo Sorci, Nadia Raffaelli
Summary: Extracellular NAD serves as a key signaling molecule in different physiological and pathological conditions, regulated by a variety of enzymes. The enzymatic activities involved in extracellular NAD metabolism play important roles in controlling immune responses, inflammatory processes, tumorigenesis, and other diseases. Further research is needed to explore the therapeutic potential of these enzymes as targets for various human diseases.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Natalia Pontes Bona, Mayara Sandrielly Pereira Soares, Nathalia Stark Pedra, Luiza Spohr, Francieli da Silva dos Santos, Alana Seixas de Farias, Fernando Lopez Alvez, Bernardo de Moraes Meine, Karina Pereira Luduvico, Roselia Maria Spanevello, Francieli Moro Stefanello
Summary: Tannic acid (TA) plays an important role in the treatment of glioblastoma, as it modulates purinergic and redox systems.
NEUROCHEMICAL RESEARCH
(2022)
Article
Gastroenterology & Hepatology
Arthur J. Kastl, Kimberly N. Weaver, Xian Zhang, Jennifer A. Strople, Jeremy Adler, Marla C. Dubinsky, Athos Bousvaros, Runa Watkins, Xiangfeng Dai, Wenli Chen, Raymond K. Cross, Peter D. R. Higgins, Ryan C. Ungaro, Meenakshi Bewtra, Emanuelle A. Bellaguarda, Francis A. Farraye, Kelly Y. Chun, Michael Zikry, Manory Fernando, Monique Bastidas, Cristian G. Hernandez, Riley G. Craig, Margie E. Boccieri, Anne Firestine, Millie D. Long, Michael D. Kappelman
Summary: Children with IBD show a robust immune response to COVID-19 vaccination with low adverse events, providing a high level of reassurance to the medical community and patients.
AMERICAN JOURNAL OF GASTROENTEROLOGY
(2023)
Review
Oncology
Federica Costa, Valentina Marchica, Paola Storti, Fabio Malavasi, Nicola Giuliani
Summary: Despite the debated use of PD-L1/PD-1 blockade in multiple myeloma (MM) patients, data on PD-1/PD-L1 expression profile and its potential link with CD38 pathways suggests a combined therapeutic approach could improve anti-tumoral effects in MM patients. Further studies are needed to clarify discrepancies in PD-1/PD-L1 distribution within the bone marrow microenvironment and to determine the efficacy of PD-1/PD-L1 blockade in reversing myeloma immune suppression and inhibiting myeloma cell survival.
Review
Immunology
Fabio Morandi, Federica Sabatini, Marina Podesta, Irma Airoldi
Summary: Neuroblastoma is a common pediatric solid tumor with varying clinical courses, and high-risk patients face poor long-term outcomes and morbidities. Adoptive cell therapy, particularly NK cells and CAR T cells, shows promise in improving the lifespan of these high-risk patients. Future prospects include gamma delta T lymphocytes and CAR NK cells.
Article
Hematology
Fabio Malavasi, Angelo C. Faini, Fabio Morandi, Barbara Castella, Danny Incarnato, Salvatore Oliviero, Alberto L. Horenstein, Massimo Massaia, Niels W. C. J. van de Donk, Paul G. Richardson
Summary: This study explored the multiple functions of CD38 and the effects of therapeutic antibodies on membrane dynamics and gene expression in multiple myeloma cells. The exposure to anti-CD38 antibodies resulted in changes in metabolism-related and cell cycle-related genes, as well as modulation of microRNA expression. Microvesicles released from the antibody-exposed cells showed alterations in both protein expression and microRNA levels, suggesting a potential role in intercellular signaling and immune response modulation. The findings provide insights on the potential mechanisms for enhancing the efficacy of anti-CD38 therapeutic antibodies.
BRITISH JOURNAL OF HAEMATOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Valentina Marchica, Federica Costa, Gaetano Donofrio, Nicola Giuliani
Summary: Multiple myeloma is a hematologic malignancy that depends on the microenvironment, and despite improvements in survival with new drugs, drug resistance and relapse remain issues, necessitating the development of new treatment strategies. Oncolytic virotherapy shows promise in cancer treatment, with various human viruses being studied in preclinical models and in clinical trials for MM patients, while the use of non-human viruses is also being explored to potentially avoid immune responses that could reduce efficacy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Danilo Marimpietri, Irma Airoldi, Angelo Corso Faini, Fabio Malavasi, Fabio Morandi
Summary: Extracellular vesicles play a significant role in cancer, transporting specific cargoes and regulating cellular activities in normal and tumor tissues. Their ability to interact with the tumor microenvironment and modulate anti-tumor immune response, tumorigenesis, tumor growth, metastasis and drug resistance highlights their potential clinical relevance.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Immunology
Fabio Morandi, Alberto Leonardo Horenstein, Fabio Malavasi
Summary: NAD(+) is a crucial molecule in metabolic processes, with CD38 playing a key role in immunosuppression in various types of tumors.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Cell Biology
Claudia Cocco, Fabio Morandi, Irma Airoldi
Summary: The tumor microenvironment is a complex network involving tumor cells and various components such as immune, stromal, and vascular endothelial cells, as well as the extracellular matrix. Signals and interactions within this environment can lead to tumor growth and metastasis, as well as the establishment of an immunosuppressive environment. Immune checkpoints play a crucial role in controlling T cell activation and anti-cancer activities within this environment, making them promising targets for therapy development.
Article
Immunology
Gaetano Donofrio, Valentina Franceschi, Francesca Macchi, Luca Russo, Anna Rocci, Valentina Marchica, Federica Costa, Nicola Giuliani, Carlo Ferrari, Gabriele Missale
Summary: COVID-19, caused by the highly infectious coronavirus SARS-CoV-2, is a global ongoing pandemic that has triggered intense scientific research on developing vaccines. Efforts are focused on quantifying neutralizing antibodies induced by vaccination to validate protection and control the pandemic, with a simplified neutralization assay being developed for easier implementation in medical laboratories. This innovative approach aims to improve the vaccination campaign and adapt to different coronavirus variants for enhanced efficacy.
Article
Oncology
Chiara Brignole, Veronica Bensa, Nuno A. Fonseca, Genny Del Zotto, Silvia Bruno, Ana F. Cruz, Fabiana Malaguti, Barbara Carlini, Fabio Morandi, Enzo Calarco, Patrizia Perri, Vera Moura, Laura Emionite, Michele Cilli, Francesco De Leonardis, Annalisa Tondo, Loredana Amoroso, Massimo Conte, Alberto Garaventa, Angela R. Sementa, Maria V. Corrias, Mirco Ponzoni, Joao N. Moreira, Fabio Pastorino
Summary: This study showed that cell surface NCL is expressed in NB cell lines, NB tumor cells, and BM-infiltrating NB cells. The targeted nanoparticles decorated with the F3 peptide were effective in inhibiting cell proliferation and reducing tumor growth in NB animal models. NCL may be a promising therapeutic target for NB.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2021)
Article
Nutrition & Dietetics
Fabio Morandi, Veronica Bensa, Enzo Calarco, Fabio Pastorino, Patrizia Perri, Maria Valeria Corrias, Mirco Ponzoni, Chiara Brignole
Summary: The study found that olive leaf extract (OLE) can inhibit proliferation and migration of neuroblastoma cells, and induce apoptosis.
Article
Oncology
Silvia Ravera, Tiziana Vigliarolo, Silvia Bruno, Fabio Morandi, Danilo Marimpietri, Federica Sabatini, Monica Dagnino, Andrea Petretto, Martina Bartolucci, Monica Muraca, Eleonora Biasin, Riccardo Haupt, Marco Zecca, Franca Fagioli, Daniela Cilloni, Marina Podesta, Francesco Frassoni
Summary: This study aimed to identify the mechanisms involved in accelerated aging, increased risk of second tumors, and chronic diseases in childhood cancer survivors due to chemo/radiotherapy. Biochemical and molecular analyses revealed inefficient oxidative phosphorylation, low energy status, and altered metabolism in CCS-MNCs compared with healthy controls, suggesting potential targets for pharmacological interventions to restore mitochondrial function and slow down aging-associated pathologies in CCS.
Editorial Material
Biochemistry & Molecular Biology
Fabio Morandi
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Fabio Morandi, Irma Airoldi
Summary: HLA-G is an HLA-class Ib molecule involved in tolerance establishment during pregnancy. The expression of HLA-G is restricted in adults but can be observed in tumors, where it contributes to immune escape and tumor progression. It interacts with other immune checkpoint molecules like PD-1, CTLA-4, TIM-3, IDO, and TIGIT. Clinical trials using monoclonal antibodies against HLA-G and other immune checkpoints have shown promising results in cancer patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Meeting Abstract
Oncology
Angelo Corso Faini, Barbara Castella, Alberto Horenstein, Fabio Morandi, Fabio Malavasi
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2022)
Meeting Abstract
Endocrinology & Metabolism
Alessia Angelelli, Fabio Morandi, Ignazia Prigione, Daniela Fava, Flavia Napoli, Mohamad Maghnie
HORMONE RESEARCH IN PAEDIATRICS
(2022)
