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.
Review
Cell Biology
Sheng Wang, Songsen Gao, Dexi Zhou, Xueyi Qian, Jiajie Luan, Xiongwen Lv
Summary: Extracellular ATP serves as a danger signal released by dying and damaged cells, promoting inflammation as an immunostimulatory signal. CD39 and CD73 play critical roles in liver disease by breaking down ATP into adenosine, shifting from a proinflammatory to an anti-inflammatory environment. The modification of the CD39-CD73-adenosine pathway alters the liver's response to injury and adenosine exerts different effects on liver pathophysiology through different receptors.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Review
Cell Biology
Karel P. Alcedo, Jessica L. Bowser, Natasha T. Snider
Summary: Purinergic signaling is a fundamental mechanism used by all cells to control their internal activities and interact with the environment. CD73, a key component of the purinergic system, has been studied in cancer therapy, but recent research shows its complex role in cellular homeostasis, physiological adaptation, and disease development.
TRENDS IN CELL BIOLOGY
(2021)
Article
Immunology
Jianan Zhu, Guangmin Song, Xiaobo Zhou, Ting-Li Han, Xinyang Yu, Hao Chen, Toby Mansell, Boris Novakovic, Philip N. Baker, Richard D. Cannon, Richard Saffery, Chang Chen, Hua Zhang
Summary: This study investigates the regulation of decidual natural killer (dNK) cells and fetal extravillous trophoblast (EVT) cells by CD39 and CD73 in unexplained recurrent spontaneous abortion (URSA). The findings suggest that reduced numbers of CD39(+) and CD73(+) cells at the maternal-fetal interface, potentially due to downregulated TGF-beta-mTOR-HIF-1α pathway, result in impaired ATP-adenosine metabolism and increased dNK cytotoxicity, contributing to URSA occurrences.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Cell Biology
Gilson P. Dorneles, Paula C. Teixeira, Igor M. da Silva, Lucas L. Schipper, Paulo C. Santana Filho, Luiz C. Rodrigues Junior, Cristina Bonorino, Alessandra Peres, Simone G. Fonseca, Marta C. Monteiro, Carina R. Boeck, Sarah Eller, Tiago F. Oliveira, Eliana M. Wendland, Pedro R. T. Romao
Summary: This study investigates alterations in purinergic pathways in COVID-19 patients and provides new insights into the immunopathology of the disease. The findings suggest that the purinergic signaling is dysregulated in both mild and severe COVID-19 patients, which may affect immune function. Additionally, increased T-cell apoptosis and decreased purine levels are observed in COVID-19 patients compared to healthy controls.
JOURNAL OF CELLULAR PHYSIOLOGY
(2022)
Article
Cell Biology
Desiree Forstner, Jacqueline Guettler, Beatrice A. Brugger, Freya Lyssy, Lena Neuper, Christine Daxboeck, Gerhard Cvirn, Julia Fuchs, Kristin Kraeker, Alina Frolova, Daniela S. Valdes, Christina Stern, Birgit Hirschmugl, Herbert Fluhr, Christian Wadsack, Berthold Huppertz, Olivia Nonn, Florian Herse, Martin Gauster
Summary: Tissue insults in response to inflammation, hypoxia and ischemia cause the release of ATP, which modulates various pathological processes. CD39 and CD73 are two major enzymes that convert extracellular ATP into adenosine. This study investigated the expression of CD39 and CD73 in placental tissue and their regulation in response to platelet-derived factors and oxygen conditions. The results showed that placental CD39 expression increased in preeclampsia and platelet-derived factors led to deregulated CD39 expression. CD39 overexpression decreased extracellular ATP levels and abolished the upregulation of pro-inflammatory cytokine interleukin-1 beta. These findings suggest that increased placental CD39 could be an important anti-coagulant defense mechanism of the placenta.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Jianlei Xing, Jinhua Zhang, Jinyan Wang
Summary: Adenosine, an immunosuppressive metabolite, plays a crucial role in tumor progression by promoting tumor cell activities and down-regulating anti-tumor immune responses. This review summarizes the role of the adenosine/adenosine receptor pathway in regulating tumor-infiltrating immune cells and provides insights into adenosine-targeted tumor immunotherapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Ryan J. King, Surendra K. Shukla, Chunbo He, Enza Vernucci, Ravi Thakur, Kuldeep S. Attri, Aneesha Dasgupta, Nina V. Chaika, Scott E. Mulder, Jaime Abrego, Divya Murthy, Venugopal Gunda, Camila G. Pacheco, Paul M. Grandgenett, Audrey J. Lazenby, Michael A. Hollingsworth, Fang Yu, Kamiya Mehla, Pankaj K. Singh
Summary: Metabolic alterations play a crucial role in regulating cancer aggressiveness and immune responses. This study found that elevated expression of CD73, an enzyme involved in generating adenosine, is associated with increased aggressiveness in pancreatic ductal adenocarcinoma (PDAC). Inhibiting CD73 expression led to reduced tumor growth and myeloid-derived suppressor cells (MDSC) in PDAC mouse models. Furthermore, CD73 knockdown resulted in increased IFN-gamma expression by intratumoral CD4(+) and CD8(+) T cells and decreased GM-CSF levels. Depletion of CD4(+) T cells, but not CD8(+) T cells, abolished the beneficial effects of CD73 reduction. Overall, targeting the adenosine axis presents a promising therapeutic strategy for enhancing the immune response against PDAC.
Article
Chemistry, Medicinal
Carla Fernanda Furtado Gardani, Eduardo Luiz Pedrazza, Victoria Santos Paz, Gabriele Goulart Zanirati, Jaderson Costa da Costa, Roberta Andrejew, Henning Ulrich, Juliete Nathali Scholl, Fabricio Figueiro, Liliana Rockenbach, Fernanda Bueno Morrone
Summary: This study investigated the expression of CD39 and CD73 enzymes in prostate cancer and their potential as therapeutic targets. The results showed higher levels of CD39 expression compared to CD73 in tissue samples and a correlation with Gleason score. In blood samples, CD39 expression in extracellular vesicles was significantly increased and positively correlated with ADP hydrolysis and Gleason score.
Article
Biochemistry & Molecular Biology
Markus Kellner, Bettina von Neubeck, Bastian Czogalla, Regina Feederle, Binje Vick, Irmela Jeremias, Reinhard Zeidler
Summary: CD73 inhibition, particularly with the antibody 22E6, shows great potential for cancer therapy by reducing tumor growth and interfering with chemoresistance. However, complete blocking of CD73 activity may have adverse effects.
Article
Chemistry, Medicinal
Yunshuo Zhao, Xiaotong Chen, Zhe Ding, Chuanjie He, Guanfei Gao, Sifan Lyu, Yanfeng Gao, Jiangfeng Du
Summary: This study successfully identified a CD39 inhibitor through a combination of methods, demonstrating its effectiveness in inhibiting CD39 enzyme activity and suppressing tumor cell proliferation. Understanding the binding mode and mechanism of action of the inhibitor can potentially lead to further optimization and exploration of its anticancer activity in vivo.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Oncology
Arthur Bauer, Niklas Gebauer, Juliana Knief, Lars Tharun, Nele Arnold, Armin Riecke, Konrad Steinestel, Hanno M. Witte
Summary: This study assessed the expression of CD39 and CD73 in different types of salivary gland carcinomas (SGCs) and found specific adenosine signaling patterns in different entities. Targeting the adenosine pathway may be a promising therapeutic option for selected entities.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Eleonora Timperi, Vincenzo Barnaba
Summary: CD39, along with CD73, plays a crucial role in converting adenosine triphosphate into an immunosuppressive form of adenosine in the tumor microenvironment. Environmental and genetic factors shape the expression of CD39, which has significant functions in regulating T cell activities. Studies from preclinical models to clinical trials have contributed essential insights into novel combinatorial approaches for cancer treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
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)
Article
Oncology
Hui Cong, Jian Gao, Qing Wang, Min Du, Huimin Li, Qian Li, Jin Li, Yiyi Liang, Dan Zhao, Hancao Yang, Yu Gan, Hong Tu
Summary: The overexpression of UQCRC1 in pancreatic cancer cells inhibits the cytotoxicity and infiltration of NK cells, while the knockdown of UQCRC1 enhances the cytotoxicity and chemotaxis of NK cells. UQCRC1 in pancreatic cancer cells interacts with eATP and adenosine to impair the function of NK cells, as well as to alter the balance of activating and inhibitory receptors on NK cells.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Xinting Hu, Hua Wang, Dai Yuan, Huiting Qu, Ying Li, Na Wang, Xianghua Wang, Xin Liu, Hongzhi Xu, Ya Zhang, Xin Wang
Summary: This study found a significant correlation between thyroid complications and unfavorable prognosis in WM/LPL patients. Thyroid complications were identified as independent prognostic indicators and incorporating them into the ISSWM score improved risk stratification and prognostic prediction. Subclinical hypothyroidism at an early stage predicted unfavorable outcomes.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Zheng Tian, Ming Liu, Xiaosheng Fang, Xiangxiang Zhou, Peipei Li, Ying Li, Lingyan Zhang, Fang Liu, Ya Zhang, Xin Wang
Summary: Chronic lymphocytic leukemia (CLL) exhibits heterogeneity between Chinese and European patients. In China, CLL patients have an earlier age of onset and younger patients have a higher relapse rate compared to elderly patients. Novel risk score models are developed to optimize the risk assessment and provide insights for individualized diagnosis and treatment of CLL patients.
FRONTIERS IN ONCOLOGY
(2022)
Review
Oncology
Xiaomin Chen, Xiangxiang Zhou, Xin Wang
Summary: YT521-B homology domain family member 2 (YTHDF2) is a protein that plays a role in various biological processes, including embryonic development, immune response, and tumor progression. It is involved in the proliferation, apoptosis, invasion, and migration of tumor cells, and modulates signaling pathways through m(6)A modification.
EXPERIMENTAL HEMATOLOGY & ONCOLOGY
(2022)
Review
Oncology
Zhuoya Yu, Xiangxiang Zhou, Xin Wang
Summary: Metabolic reprogramming, a hallmark of cancer progression, supports tumorigenesis and tumor progression by allowing cells to uptake essential nutrients and altering metabolic pathways to meet increased demands for energy and biosynthetic precursors. Activated oncogenes coordinate with altered metabolism to control cell-autonomous pathways, potentially leading to tumorigenesis. Targeting metabolic features of hematologic malignancies has shown promising therapeutic potential in both clinical and preclinical studies.
Article
Hematology
Wei Xu, Keshu Zhou, Tingyu Wang, Shenmiao Yang, Lihong Liu, Yu Hu, Wei Zhang, Kaiyang Ding, Jianfeng Zhou, Sujun Gao, Bing Xu, Zunmin Zhu, Ting Liu, Huilai Zhang, Jianda Hu, Chunyan Ji, Shunqing Wang, Zhongjun Xia, Xin Wang, Yan Li, Yongping Song, Shuo Ma, Xinran Tang, Bin Zhang, Jianyong Li
Summary: Orelabrutinib demonstrated significant efficacy and safety in patients with refractory or relapsed CLL/SLL, with an overall response rate of 92.5%. The median progression-free survival had not been reached at a 32.3-month median follow-up. Moreover, Orelabrutinib showed promising response in patients with high prognostic risks.
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Article
Oncology
Huishou Fan, Weida Wang, Ya Zhang, Jianxiang Wang, Tao Cheng, Lugui Qiu, Xin Wang, Zhongjun Xia, Gang An
Summary: The objective of this study was to understand the current care paradigm and outcomes of patients with newly diagnosed multiple myeloma (NDMM) in China. The study found that novel agent-based regimens, first-line autologous stem cell transplantation (ASCT), and sustained minimal residual disease (MRD) negativity were associated with a superior outcome for NDMM patients.
CANCER BIOLOGY & MEDICINE
(2023)
Article
Cell Biology
Shunfeng Hu, Tiange Lu, Juanjuan Shang, Yiqing Cai, Mengfei Ding, Xiangxiang Zhou, Xin Wang
Summary: This study found that DLBCL patients have high concentration of serum PGD2 and low expression of PGD2 receptor CRTH2, which are associated with clinical features and prognosis. Moreover, high-concentration PGD2 can inhibit DLBCL progression by regulating cell proliferation, apoptosis, cell cycle, and invasion, as well as induce DNA damage and enhance the cytotoxicity of anti-tumor drugs. Additionally, HDAC inhibitors and CRTH2 inhibitors can modulate PGD2 production and enhance their anti-tumor effects. Overall, PGD2 and CRTH2 may serve as prognostic biomarkers and therapeutic targets in DLBCL.
CELL DEATH DISCOVERY
(2023)
Article
Oncology
Xinting Hu, Yang Han, Jiarui Liu, Hua Wang, Zheng Tian, Xin Zhang, Ya Zhang, Xin Wang
Summary: In this study, it was found that the expression of CTPS2 was significantly upregulated in patients with CLL and was closely associated with poor prognostic indicators. Downregulation of CTPS2 in CLL cells inhibited cell proliferation, induced cell cycle arrest and increased apoptosis. Further research revealed that CTPS2 promoted CLL progression by regulating the DNA damage response and repair pathway through interaction with the BRCA1 protein. These findings suggest that targeting nucleotide metabolism could be a promising strategy for CLL treatment.
EXPERIMENTAL HEMATOLOGY & ONCOLOGY
(2023)
Article
Oncology
Yiqing Cai, Xiaomin Chen, Tiange Lu, Zhuoya Yu, Shunfeng Hu, Jiarui Liu, Xiangxiang Zhou, Xin Wang
Summary: The mRNA and protein levels of TMEM173 are increased in B-ALL patients, and its expression is higher in specific cells. Targeted activation of TMEM173 may provide new therapeutic strategies for B-ALL.
Article
Genetics & Heredity
Xin Zhang, Yang Han, Yu Nie, Yujie Jiang, Xiaohui Sui, Xueling Ge, Fang Liu, Ya Zhang, Xin Wang
Summary: This study reveals the prognostic value of PAX5 in mantle cell lymphoma and establishes a new risk scoring system, MIPI-SP, which outperforms the MIPI score in predicting prognosis.
JOURNAL OF MOLECULAR MEDICINE-JMM
(2023)
Article
Oncology
Yurou Chu, Yingyue Liu, Yujie Jiang, Xueling Ge, Dai Yuan, Mei Ding, Huiting Qu, Fang Liu, Xiangxiang Zhou, Xin Wang
Summary: This study evaluated the predictive value of systemic inflammation response index (SIRI) in primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL) patients and established a highly discriminating risk prediction model. The presence of high pretreatment SIRI was significantly associated with poorer survival and identified as an independent prognostic factor. A new model, SIRI-PI, showed superior performance in predicting high-risk assessment compared to NCCN-IPI.
Article
Hematology
Li-Juan Deng, Ke-Shu Zhou, Li-Hong Liu, Ming-Zhi Zhang, Zhi-Ming Li, Chun-Yan Ji, Wei Xu, Ting Liu, Bing Xu, Xin Wang, Su-Jun Gao, Hui-Lai Zhang, Yu Hu, Yan Li, Ying Cheng, Hai-Yan Yang, Jun-Ning Cao, Zun-Min Zhu, Jian-Da Hu, Wei Zhang, Hong-Mei Jing, Kai-Yang Ding, Xiang-Yang Zhang, Ren -Bin Zhao, Bin Zhang, Ya -Min Tian, Yong-Ping Song, Yu-Qin Song, Jun Zhu
Summary: Orelabrutinib demonstrates significant efficacy and tolerability in patients with relapsed or refractory mantle cell lymphoma, with a high overall response rate and median progression-free survival.
Article
Cell Biology
Yiqing Cai, Liemei Lv, Tiange Lu, Mengfei Ding, Zhuoya Yu, Xiaomin Chen, Xiangxiang Zhou, Xin Wang
Summary: Metabolic reprogramming, specifically dysregulation of glutamine metabolism, plays a crucial role in tumorigenesis, microenvironment remodeling, and therapeutic resistance in DLBCL. High levels of glutamine are associated with poor clinical outcomes, while the derivative of glutamine, a-KG, is negatively correlated with invasiveness features. Treatment with DM-aKG significantly inhibits tumor growth by inducing apoptosis and non-apoptotic cell death. The study highlights the potential use of a-KG as a novel therapeutic strategy for DHL patients.
CELL DEATH DISCOVERY
(2023)
Article
Nutrition & Dietetics
Tiange Lu, Xue Shi, Xueling Ge, Ying Li, Yiqing Cai, Xiaomin Chen, Shunfeng Hu, Mei Ding, Xiaosheng Fang, Fang Liu, Xiangxiang Zhou, Xin Wang
Summary: In this study, the significance of nutritional status in extranodal NK/T-cell lymphoma (ENKTL) was explored, and a new scoring system (CONUT-PINK-E) was developed to assess patients' nutritional status and prognosis. The results showed that CONUT-PINK-E could independently predict patients' overall survival and progression-free survival, and presented superior discrimination and clinical benefit compared to current models.
FRONTIERS IN NUTRITION
(2023)
Article
Biochemistry & Molecular Biology
Xiaomin Chen, Tiange Lu, Yiqing Cai, Yang Han, Mengfei Ding, Yurou Chu, Xiangxiang Zhou, Xin Wang
Summary: The study reveals that m6A modification mediated by KIAA1429 plays a role in DLBCL progression by regulating CHST11 expression and inactivating the Hippo-YAP pathway. KIAA1429 has the potential to be a predictive biomarker and therapeutic target for DLBCL.
CELLULAR & MOLECULAR BIOLOGY LETTERS
(2023)