Review
Oncology
Anneloes van Duijn, Sjoerd H. Van der Burg, Ferenc A. Scheeren
Summary: This article focuses on the interactions between myeloid immune cells and anti-tumor immune responses in the tumor microenvironment. Blocking the CD47/SIRP alpha axis can enhance adaptive immune response. The potential therapeutic role of CD47/SIRP alpha axis is discussed in tumors with acquired resistance to classic immunotherapy.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Oncology
Rama Krishna Narla, Hardik Modi, Daniel Bauer, Mahan Abbasian, Jim Leisten, Joseph R. Piccotti, Stephan Kopytek, Brendan P. Eckelman, Quinn Deveraux, John Timmer, Dan Zhu, Lilly Wong, Laure Escoubet, Heather K. Raymon, Kandasamy Hariharan
Summary: CD47, overexpressed on tumor cells, inhibits phagocytosis by macrophages, while CC-90002, a humanized anti-CD47 antibody, enhances phagocytosis of tumor cells and inhibits tumor growth by recruiting macrophages to bind with tumor cells.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2022)
Article
Medicine, Research & Experimental
Yiqing Li, Hui Zhou, Pan Liu, Dandan Lv, Yichun Shi, Bufu Tang, Jiaqi Xu, Tingting Zhong, Wangting Xu, Jie Zhang, Jianying Zhou, Kejing Ying, Yongchao Zhao, Yi Sun, Zhinong Jiang, Hongqiang Cheng, Xue Zhang, Yuehai Ke
Summary: The CD47/SIRPα axis requires deneddylation of SHP2 for controlling tumor-infiltrating macrophages. Deneddylation of SHP2 leads to inhibition of macrophage phagocytosis and enhances the efficacy of colorectal cancer immunotherapy.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Chemistry, Medicinal
Yehong Tan, Hanhua Chen, Jie Zhang, Linxiang Cai, Suxing Jin, Dongfan Song, Tao Yang, Zijian Guo, Xiaoyong Wang
Summary: The platinum-based immunomodulators MUP and DMUP were synthesized to enhance the phagocytic activity of macrophages by blocking the CD47-SIRPa axis. They showed high antiproliferative activity against human cancer cells and cooperated with PBMCs to suppress cancer cells. DMUP, in particular, decreased CD47 expression in tumor tissues and promoted the polarization of macrophages, leading to enhanced anticancer effects.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Medicine, Research & Experimental
Satoka Shiratori-Aso, Daigo Nakazawa, Takashi Kudo, Masatoshi Kanda, Yusho Ueda, Kanako Watanabe-Kusunoki, Saori Nishio, Sari Iwasaki, Takahiro Tsuji, Sakiko Masuda, Utano Tomaru, Akihiro Ishizu, Tatsuya Atsumi
Summary: Neutrophil extracellular trap (NET) formation is an important part of immune defense and cell death. Excessive NET formation can be found in patients with anti-neutrophil cytoplasmic antibody-associated (ANCA-associated) vasculitis (AAV), leading to disease progression. The CD47 signaling pathway plays a role in the escape of pathogenic NETs from efferocytosis, resulting in the development of necrotizing vasculitis. Inhibition of CD47 can protect against glomerulonephritis in AAV by restoring efferocytosis of ANCA-induced NETs.
Article
Chemistry, Multidisciplinary
Jia-Qi Luo, Rong Liu, Fang-Man Chen, Jing-Yang Zhang, Sui-Juan Zheng, Dan Shao, Jin-Zhi Du
Summary: A degradable mesoporous silica nanoparticle (MSN) has been developed for simultaneous delivery of anti-CD47 antibodies (aCD47) and doxorubicin (DOX) in cancer chemo-immunotherapy. The nanocarrier, aCD47-DMSN, blocks the CD47-SIRP alpha axis and induces immunogenic tumor cell death for enhanced phagocytosis by macrophages. This study provides a promising nanoplatform for modulating macrophage phagocytosis in cancer therapy.
Review
Immunology
Yu Hao, Xinxuan Zhou, Yiling Li, Bolei Li, Lei Cheng
Summary: Cluster of differentiation 47 (CD47) is a transmembrane protein that is widely present on cell surfaces and overexpressed by cancer cells. It interacts with signal-regulatory protein a (SIRPa) to inhibit macrophage-mediated phagocytosis and achieve immune escape. Targeting the CD47-SIRPa axis as a cancer immunotherapy has shown promising results in pre-clinical studies.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Oncology
Huanpeng Chen, Yuying Yang, Yuqing Deng, Fengjiao Wei, Qingyu Zhao, Yongqi Liu, Zhonghua Liu, Bolan Yu, Zhaofeng Huang
Summary: This study developed CAR-T cells that can secrete a CD47 blocker, enhancing the therapeutic efficacy of CAR-T cells in solid tumor therapy. The results showed that these CAR-T cells significantly reduced tumor burden, prolonged survival, and modulated the tumor microenvironment.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Medicine, Research & Experimental
Sean K. Wang, Yunlu Xue, Constance L. Cepko
Summary: Microglial phagocytosis is upregulated during cone degeneration in retinitis pigmentosa, suggesting that the expression of the CD47 signal may protect cones. Augmentation of CD47/SIRP alpha signaling could be a potential treatment strategy for RP and other forms of neurodegeneration.
Article
Oncology
Mark A. J. M. Hendriks, Isabel Britsch, Xiurong Ke, Anne P. van Wijngarden, Douwe F. Samplonius, Emily M. Ploeg, Wijnand Helfrich
Summary: Cancer cells use overexpression of CD47 to inhibit immune cell clearance and new antigen processing, as well as to evade T cell immune attack through CD47 expression. However, knocking out CD47 makes cancer cells more susceptible to T cell attack. A bispecific antibody has been designed to overcome CD47-mediated immune resistance and enhance cancer cell susceptibility to T cell attack.
Article
Oncology
Ewa Cendrowicz, Lisa Jacob, Shirley Greenwald, Ami Tamir, Iris Pecker, Rinat Tabakman, Lucy Ghantous, Liat Tamir, Roy Kahn, Jasmine Avichzer, Alexandra Aronin, Shira Amsili, Elina Zorde-Khvalevsky, Yosi Gozlan, Martijn Vlaming, Gerwin Huls, Tom van Meerten, Michal Elhalel Dranitzki, Adam Foley-Comer, Yaron Pereg, Amnon Peled, Ayelet Chajut, Edwin Bremer
Summary: DSP107 effectively (re)activates innate and adaptive anticancer immune responses and may be of therapeutic use alone and in combination with rituximab for the treatment of DLBCL patients.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Review
Cell Biology
Amy Xiao, Oleg E. Akilov
Summary: The loss of CD47 on aging cells signals macrophages to eliminate the target. CD47 acts as a "do-not-eat-me" sign that prevents macrophagal phagocytosis by interacting with its ligand SIRP alpha. Malignant lymphocytes highly express CD47, making them ideal candidates for targeted anti-CD47 therapies. There are various types of anti-CD47-SIRP alpha therapeutic molecules, including monoclonal antibodies, bioengineered proteins, miRNAs, and bispecific antibodies. Blocking the CD47-SIRP alpha axis in combination with targeting secondary tumor microenvironment (TME) may enhance the effectiveness of current immunotherapeutic approaches.
Article
Hematology
Megan M. Dacek, Keifer G. Kurtz, Patrick Wallisch, Stephanie A. Pierre, Shireen Khayat, Christopher M. Bourne, Thomas J. Gardner, Kristen C. Vogt, Nica Aquino, Anas Younes, David A. Scheinberg
Summary: Chimeric antigen receptor (CAR) T-cell therapy combined with local CD47 blockade and an orthogonal antibody may be a promising combinatorial strategy to enhance the effectiveness of hematopoietic malignancy treatment. In this study, Orexi CAR T cells were engineered to secrete a high-affinity CD47 blocker, CV1, at the tumor site, leading to an additive effect in xenograft models when combined with an orthogonally targeted monoclonal antibody. Furthermore, the local secretion of CV1 reversed the immunosuppression of myelomonocytoid cells in both in vitro and tumor microenvironment settings.
Article
Oncology
Veronika Lysenko, Patrick M. Schurch, Selma Tuzlak, Nicole Wildner-Verhey van Wijk, Larisa V. Kovtonyuk, Burkhard Becher, Markus G. Manz, Stefanie Kreutmair, Alexandre P. A. Theocharides
Summary: Polycythemia vera (PV) is a hematopoietic stem cell neoplasm driven by JAK2 mutations that result in uncontrolled red blood cell (RBC) production. Blocking the CD47-SIRP alpha interaction can correct the polycythemia phenotype in a PV mouse model.
Article
Oncology
Siret Tahk, Binje Vick, Bjoern Hiller, Saskia Schmitt, Anetta Marcinek, Enrico D. Perini, Alexandra Leutbecher, Christian Augsberger, Anna Reischer, Benjamin Tast, Andreas Humpe, Irmela Jeremias, Marion Subklewe, Nadja C. Fenn, Karl-Peter Hopfner
Summary: The SIRP alpha-alpha CD123 fusion antibodies show promising therapeutic effects for AML by combining local CD47 blockade with specific LSC targeting, effectively eliminating AML LSCs while minimizing the risk of targeting healthy cells.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Hongxue Shi, Russell A. Prough, Craig J. McClain, Ming Song
Summary: This study aimed to investigate the combined effects of different types of dietary fat and fructose on the development of NAFLD in a murine model. Results showed that mice fed with high-saturated fat diet exhibited severe hepatic steatosis and liver injury, while fructose supplementation exacerbated liver fibrosis. Mice fed with omega-6 polyunsaturated fat diet combined with fructose showed impaired glucose tolerance. In summary, excessive intake of fat and fructose has negative effects on liver health.
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
(2023)
Article
Gastroenterology & Hepatology
Alessandro Mantovani, Serena Pelusi, Sara Margarita, Francesco Malvestiti, Michela Dell'Alma, Cristiana Bianco, Luisa Ronzoni, Daniele Prati, Giovanni Targher, Luca Valenti
Summary: The study aimed to assess the effect of the PNPLA3 p.I148M variant on the estimated glomerular filtration rate (eGFR) in individuals with metabolic dysfunction. The results showed that this variant was associated with lower eGFR levels and faster eGFR decline. This finding is important for understanding the relationship between kidney damage and genetic susceptibility.
ALIMENTARY PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Gastroenterology & Hepatology
Yoshinobu Saito, Dingzi Yin, Naoto Kubota, Xiaobo Wang, Aveline Filliol, Helen Remotti, Ajay Nair, Ladan Fazlollahi, Yujin Hoshida, Ira Tabas, Kirk J. Wangensteen, Robert F. Schwabe
Summary: This study investigated the regulation and function of Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) in hepatocellular carcinoma (HCC). The results showed that TAZ expression was regulated by cholesterol synthesis and that it promoted HCC growth through increased tumor cell proliferation. The cholesterol-TAZ-TEAD2-ANLN/KIF23 pathway was identified as a mediator of HCC proliferation and a potential therapeutic target, which could be combined with tumor immune micro-environment (TIME)-targeted therapies.
Article
Gastroenterology & Hepatology
Jenny Lee, Max Westphal, Yasaman Vali, Jerome Boursier, Salvatorre Petta, Rachel Ostroff, Leigh Alexander, Yu Chen, Celine Fournier, Andreas Geier, Sven Francque, Kristy Wonders, Dina Tiniakos, Pierre Bedossa, Mike Allison, Georgios Papatheodoridis, Helena Cortez-Pinto, Raluca Pais, Jean-Francois Dufour, Diana Julie Leeming, Stephen Harrison, Jeremy Cobbold, Adriaan G. Holleboom, Hannele Yki-Jarvinen, Javier Crespo, Mattias Ekstedt, Guruprasad P. Aithal, Elisabetta Bugianesi, Manuel Romero-Gomez, Richard Torstenson, Morten Karsdal, Carla Yunis, Joern M. Schattenberg, Detlef Schuppan, Vlad Ratziu, Clifford Brass, Kevin Duffin, Koos Zwinderman, Michael Pavlides, Quentin M. Anstee, Patrick M. Bossuyt, LITMUS Investigators
Summary: Detection of NASH and at-risk NASH can be improved by constructing independent machine learning models for each component, using only clinical predictors. Adding biomarkers only improved the accuracy of fibrosis.
Article
Gastroenterology & Hepatology
Mary E. Rinella, Jeffrey V. Lazarus, Vlad Ratziu, Sven M. Francque, Arun J. Sanyal, Fasiha Kanwal, Diana Romero, Manal F. Abdelmalek, Quentin M. Anstee, Juan Pablo Arab, Marco Arrese, Ramon Bataller, Ulrich Beuers, Jerome Boursier, Elisabetta Bugianesi, Christopher D. Byrne, Graciela E. Castro Narro, Abhijit Chowdhury, Helena Cortez-Pinto, Donna R. Cryer, Kenneth Cusi, Mohamed El-Kassas, Samuel Klein, Wayne Eskridge, Jiangao Fan, Samer Gawrieh, Cynthia D. Guy, Stephen A. Harrison, Seung Up Kim, Bart G. Koot, Marko Korenjak, Kris V. Kowdley, Florence Lacaille, Rohit Loomba, Robert Mitchell-Thain, Timothy R. Morgan, Elisabeth E. Powell, Michael Roden, Manuel Romero-Gomez, Marcelo Silva, Shivaram Prasad Singh, Silvia C. Sookoian, C. Wendy Spearman, Dina Tiniakos, Luca Valenti, Miriam B. Vos, Vincent Wai-Sun Wong, Stavra Xanthakos, Yusuf Yilmaz, Zobair Younossi, Ansley Hobbs, Marcela Villota-Rivas, Philip N. Newsome
Summary: This study aimed to determine if there was a need to change the nomenclature and definition of NAFLD and NASH. Through a Delphi process involving content experts and patient advocates, a consensus was reached to replace NAFLD with metabolic dysfunction-associated steatotic liver disease (MetALD) and modify the diagnostic criteria. The new nomenclature and criteria are widely supported, nonstigmatizing, and can improve awareness and patient identification.
Review
Immunology
Maaike Schilperoort, David Ngai, Santosh R. Sukka, Kleopatra Avrampou, Hongxue Shi, Ira Tabas
Summary: The process of macrophages engulfing dying cells, known as efferocytosis, is tightly regulated and involves sensing, binding, engulfment, and digestion of apoptotic cells. Efferocytosis not only prevents tissue necrosis and inflammation caused by secondary necrosis of dying cells, but also promotes pro-resolving signaling in macrophages, which is essential for tissue resolution and repair following injury or inflammation. The cargo released from apoptotic cells after their engulfment and digestion by macrophages, containing amino acids, nucleotides, fatty acids, and cholesterol, plays a crucial role in this pro-resolving reprogramming.
IMMUNOLOGICAL REVIEWS
(2023)
Article
Biochemistry & Molecular Biology
Melissa Tomasi, Alessandro Cherubini, Serena Pelusi, Sara Margarita, Cristiana Bianco, Francesco Malvestiti, Lorenzo Miano, Stefano Romeo, Daniele Prati, Luca Valenti
Summary: This study investigates the relationship between circulating IL32 concentration and blood pressure control in individuals at high risk of metabolic dysfunction associated fatty liver disease (MAFLD). The results show that higher IL32 levels are independently associated with impaired blood pressure control, indicating a close association between IL32 concentration and cardiovascular disease risk.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Endocrinology & Metabolism
Luca Valenti, Elena Corradini, Leon A. Adams, Elmar Aigner, Saleh Alqahtani, Marco Arrese, Edouard Bardou-Jacquet, Elisabetta Bugianesi, Jose-Manuel Fernandez-Real, Domenico Girelli, Hannes Hagstrom, Benjamin Henninger, Kris Kowdley, Guido Ligabue, Donald McClain, Fabrice Laine, Koji Miyanishi, Martina U. Muckenthaler, Alessia Pagani, Patrizia Pedrotti, Antonello Pietrangelo, Daniele Prati, John D. Ryan, Laura Silvestri, C. Wendy Spearman, Per Stal, Emmanuel A. Tsochatzis, Francesca Vinchi, Ming-Hua Zheng, Heinz Zoller
Summary: Hyperferritinaemia is often associated with metabolic dysfunction and fatty liver and is linked to an increased risk of cardiometabolic and liver diseases. The main determinants of ferritin levels in individuals with metabolic dysfunction are genetic variants that affect iron metabolism. However, there is currently a lack of validated criteria for the diagnosis and staging of metabolic hyperferritinaemia, and the benefits of iron depletion therapy remain unclear. In this article, the authors provide an overview of the relationship between hyperferritinaemia and iron accumulation in individuals with metabolic dysfunction and propose updated definitions and staging systems, highlighting research gaps and suggesting future study designs and outcome measures.
NATURE REVIEWS ENDOCRINOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Alessandro Mantovani, Chiara Zusi, Alessandro Csermely, Antonio Taverna, Davide Cappelli, Micol Pagani, Luca Valenti, Claudio Maffeis, Giovanni Targher
Summary: This study found that the PNPLA3 rs738409 variant is associated with a decline in estimated glomerular filtration rate (eGFR) in individuals with type 2 diabetes. In a 5-year follow-up of post-menopausal women, those with the rs738409 CG/GG genotypes had a faster eGFR decline. This association remained significant even after adjusting for common renal risk factors and certain glucose-lowering medications.
NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES
(2023)
Editorial Material
Gastroenterology & Hepatology
Luca Valenti, Elia Casirati
ALIMENTARY PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Gastroenterology & Hepatology
Jeffrey V. Lazarus, Henry E. Mark, Alina M. Allen, Juan Pablo Arab, Patrizia Carrieri, Mazen Noureddin, William Alazawi, Naim Alkhouri, Saleh A. Alqahtani, Quentin M. Anstee, Marco Arrese, Ramon Bataller, Thomas Berg, Paul N. Brennan, Patrizia Burra, Graciela E. Castro-Narro, Helena Cortez-Pinto, Kenneth Cusi, Nikos Dedes, Ajay Duseja, Sven M. Francque, Amalia Gastaldelli, Hannes Hagstrom, Terry T. K. Huang, Dana Ivancovsky Wajcman, Achim Kautz, Christopher J. Kopka, Aleksander Krag, Philip N. Newsome, Mary E. Rinella, Diana Romero, Shiv Kumar Sarin, Marcelo Silva, C. Wendy Spearman, Norah A. Terrault, Emmanuel A. Tsochatzis, Luca Valenti, Marcela Villota-Rivas, Shira Zelber-Sagi, Joern M. Schattenberg, Vincent Wai-Sun Wong, Zobair M. Younossi
Summary: Fatty liver disease is a major public health threat, and focused interventions are urgently needed. A consensus-driven action agenda has been developed, which includes 29 priorities such as early diagnosis, addressing the needs of patients with multiple morbidities, and incorporating fatty liver disease into non-communicable disease strategies and guidance.
Article
Biochemistry & Molecular Biology
Alessandro Cherubini, Mahnoosh Ostadreza, Oveis Jamialahmadi, Serena Pelusi, Eniada Rrapaj, Elia Casirati, Giulia Passignani, Marjan Norouziesfahani, Elena Sinopoli, Guido Baselli, Clara Meda, Paola Dongiovanni, Daniele Dondossola, Neil Youngson, Aikaterini Tourna, Shilpa Chokshi, Elisabetta Bugianesi, Sara Della Torre, Daniele Prati, Stefano Romeo, Luca Valenti
Summary: Fatty liver disease caused by metabolic dysfunction is a leading liver disease, and women may be more susceptible to developing rapidly progressive fatty liver disease during menopause. A study has found that there is a specific interaction between female sex and the PNPLA3 gene variant in determining fatty liver disease in women.
Article
Gastroenterology & Hepatology
Gong Feng, Luca Valenti, Vincent Wai-Sun Wong, Yasser Mahrous Fouad, Yusuf Yilmaz, Won Kim, Giada Sebastiani, Zobair M. Younossi, Virginia Hernandez-Gea, Ming-Hua Zheng
Summary: This article discusses the importance of recompensation in the field of cirrhosis, particularly in NAFLD-related cirrhosis. It provides an up-to-date perspective on the natural history of NAFLD, emphasizing its reversible nature, and discusses the mechanisms and challenges of recompensation, as well as outlining future research directions.
NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY
(2023)
Editorial Material
Gastroenterology & Hepatology
Luca V. C. Valenti, Vittoria Moretti
Summary: Metabolic dysfunction-associated steatotic liver disease (MASLD) has a strong heritable component, and new inherited variants that modulate the risk of MASLD have been identified. These findings improve our understanding of disease pathogenesis and enable the development of precision medicine approaches.
NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY
(2023)
Article
Medicine, General & Internal
Damiano Baldassarre, Licia Iacoviello, Roberta Baetta, Maria Carla Roncaglioni, Gianluigi Condorelli, Giuseppe Remuzzi, Gianfranco Gensini, Luigi Frati, Walter Ricciardi, Pier Giulio Conaldi, Antonio Uccelli, Fabio Blandini, Silvano Bosari, Giovanni Scambia, Massimo Fini, Antonio Di Malta, Mauro Amato, Fabrizio Veglia, Alice Bonomi, Catherine Klersy, Francesca Colazzo, Martino Pengo, Francesca Gorini, Luciana Auteri, Giuseppe Ferrante, Marta Baviera, Giuseppe Ambrosio, Alberico Catapano, Alessandro Gialluisi, Alexis Elias Malavazos, Serenella Castelvecchio, Massimiliano Marco Corsi-Romanelli, Rosanna Cardani, Maria Teresa La Rovere, Valentina Agnese, Bianca Pane, Daniele Prati, Laura Spinardi, Giovanna Liuzzo, Eloisa Arbustini, Maurizio Volterrani, Marco Visconti, Jose Pablo Werba, Stefano Genovese, Grzegorz Bilo, Cecilia Invitti, Anna Di Blasio, Carolina Lombardi, Andrea Faini, Debora Rosa, Luisa Ojeda-Fernandez, Andreana Foresta, Amalia De Curtis, Augusto Di Castelnuovo, Simonetta Scalvini, Antonia Pierobon, Alessandra Gorini, Luca Valenti, Livio Luzi, Annarosa Racca, Manuela Bandi, Elena Tremoli, Lorenzo Menicanti, Gianfranco Parati, Giulio Pompilio
Summary: The CV-PREVITAL study is a multicentre, prospective, randomised, controlled, open-label interventional trial aiming to compare the effectiveness of an educational and motivational mobile health intervention with usual care in reducing cardiovascular risk. The trial plans to enrol approximately 80,000 subjects without overt cardiovascular diseases and evaluate the short-term endpoints, as well as conduct a long-term follow-up to assess the incidence of major adverse cardiovascular events.