Foxp3+ regulatory T ( Treg) cells promote tumor growth by various mechanisms and induce immuno-senescence. The novel immune checkpoint coinhibitory receptor T cell Ig and ITIM domain (TIGIT) shares similar ligands as the costimulatory receptor DNAX accessory molecule 1 (DNAM-1) and suppresses T cell responses in tumor patients. This study is aimed at characterizing whether the TIGIT/DNAM-1 axis is involved in the distribution and expression of Foxp3+ Treg cell subsets in acute myeloid leukemia (AML) patients of different clinical statuses: AML (27 patients), AML in nonremission (NR) (7 patients), and AML in complete remission (CR) (12 patients). Our data demonstrated that the proportions of Foxp3+, TIGIT+Foxp3+, and DNAM-1+Foxp3+ T cells are significantly higher in and NR patients. High levels of TIGIT and DNAM-1 on Foxp3+ T cells correlated with increased Foxp3+ T cell frequencies. In addition, a high TIGIT/DNAM-1 ratio was observed in AML patients and healthy individuals (HIs). Furthermore, the phenotypic abnormalities in Foxp3+, TIGIT+Foxp3+, and DNAM-1+Foxp3+ T cells were restored when the patients achieved CR after chemotherapy. Moreover, higher TIGIT+Foxp3+ T cells were associated with AML patients who had poor overall survival and were an independent risk factor for prognosis. In conclusion, our study reveals for the first time that the TIGIT/DNAM-1 axis may be involved in Foxp3+ Treg cells and indicates the clinical progression and prognosis of AML patients of different clinical statuses, which is considered beneficial for efficient AML immunotherapy.
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http://dx.doi.org/10.1155/2020/4612952 | DOI Listing |
Cell Commun Signal
January 2025
Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Provincial Key Laboratory of Biotechnology, College of Life Sciences, Northwest University, Xi'an, P. R. China.
Fat mass and obesity-associated protein (FTO) was the first m6A demethylase identified, which is responsible for eliminating m6A modifications in target RNAs. While it is well-established that numerous cytosolic and nuclear proteins undergo O-GlcNAcylation, the possibility of FTO being O-GlcNAcylated and its functional implications remain unclear. This study found that a negative correlation between FTO expression and O-GlcNAcylation in patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML).
View Article and Find Full Text PDFPharmacoecon Open
January 2025
HTA & Pharmaceutical Economics Department, Italian Medicines Agency (AIFA), Rome, Italy.
Background: The authorization of new therapeutic indications for drugs already reimbursed by the Italian National Health Service (NHS) represents a matter of importance. This study aims to estimate the additional discount attributed to the extension of indications (EoIs) to explore the potential correlation between spending and negotiated discounts and to find specific factors (determinants) that impact on discount.
Methods: The study focused on drugs approved in Italy between 2003 and 2017 with at least four therapeutic indications, including the first approved and EoIs, with follow-up extended until 2021 to acquire all the information on the negotiation process that has been completed.
Front Immunol
January 2025
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
Introduction: Hematopoietic stem cell transplantation (HSCT) and chemotherapy are considered potentially curative options for post-remission therapy in acute myeloid leukemia (AML). However, the comparative effectiveness of these approaches in favorable- and intermediate-risk AML remains unclear and requires further investigation.
Methods: In this retrospective study, 111 patients diagnosed with de novo favorable- and intermediate-risk AML, categorized according to the ELN 2022 guidelines, were investigated to compare outcomes following autologous HSCT (auto-HSCT), matched sibling donor HSCT (MSD-HSCT), and chemotherapy.
Lancet Reg Health Eur
March 2025
Department of Haematology, Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark.
Background: Second primary malignancies (SPMs) are a well-known, long-term complication of antineoplastic treatment. This nationwide cohort study examined the risk of non-myeloid SPMs in survivors of adult acute myeloid leukaemia (AML) treated with intensive chemotherapy and, in some cases, allogeneic stem cell transplantation (alloSCT), compared to a matched general population.
Methods: Patients with incident AML between 2000 and 2018, alive and aged 18-70 years two years after start of intensive chemotherapy, were included and matched 1:10 to comparators from the general Danish population on sex, age, and the Nordic Multimorbidity Index.
Mol Med
January 2025
Nanjing Women and Children's Healthcare Hospital, Maternal and Child Health Institute, Women's Hospital of Nanjing Medical University, 123 Tianfei Alley, Mochou Road, Nanjing, China.
Proteins that bind to DNA/RNA are typically evolutionarily conserved with multiple regulatory functions in transcription initiation, mRNA translation, stability of RNAs, and RNA splicing. Therefore, dysregulation of DNA/RNA binding proteins such as purine-rich element binding protein alpha (PURα) disrupts signaling transduction and often leads to human diseases including cancer. PURα was initially recognized as a tumor suppressor in acute myeloid leukemia (AML) and prostate cancer (PC).
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