Chronic lymphocytic leukemia (CLL) is characterized by the expansion of malignant CD5 B lymphocytes in blood, bone marrow, and lymphoid organs. CD1d-restricted invariant natural killer T (iNKT) cells are innate-like T lymphocytes strongly implicated in tumor surveillance. We investigated the impact of iNKT cells in the natural history of the disease in the Eμ-Tcl1 (Tcl1) CLL mouse model and 68 CLL patients. We found that Tcl1-CLL cells express CD1d and that iNKT cells critically delay disease onset but become functionally impaired upon disease progression. In patients, disease progression correlates with high CD1d expression on CLL cells and impaired iNKT cells. Conversely, disease stability correlates with negative or low CD1d expression on CLL cells and normal iNKT cells, suggesting indirect leukemia control. iNKT cells indeed hinder CLL survival in vitro by restraining CD1d-expressing nurse-like cells, a relevant proleukemia macrophage population. Multivariable analysis identified iNKT cell frequency as an independent predictor of disease progression. Together, these results support the contribution of iNKT cells to CLL immune surveillance and highlight iNKT cell frequency as a prognostic marker for disease progression.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1182/blood-2016-11-751065 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Immune cells determine the role of the tumor microenvironment during tumor progression, either suppressing tumor formation or promoting tumorigenesis. We analyzed the profile of immune cells in the tumor microenvironment of control mouse skins and skin tumors at the single-cell level. We identified 15 CD45 immune cell clusters, which broadly represent the most functionally characterized immune cell types including macrophages, Langerhans cells (LC), conventional type 1 dendritic cells (cDC1), conventional type 2 dendritic cells (cDC2), migratory/mature dendritic cells (mDC), dendritic epidermal T cells (DETC), dermal γδ T cells (γδT), T cells, regulatory T cells (Tregs), natural killer cells (NK), type 2 innate lymphoid cells (ILC2), neutrophils (Neu), mast cells (Mast), and two proliferating populations (Prolif.
View Article and Find Full Text PDFAcute myeloid leukemia (AML) that is relapsed and/or refractory post-allogeneic hematopoietic cell transplantation (HCT) is usually fatal. In a prior study, we demonstrated that AML relapse in high-risk patients was prevented by post-HCT immunotherapy with Epstein-Barr virus (EBV)-specific donor CD8 T cells engineered to express a high-affinity Wilms Tumor Antigen 1 (WT1)-specific T-cell receptor (TTCR- C4). However, in the present study, infusion of EBV- or Cytomegalovirus (CMV)-specific T did not clearly improve outcomes in fifteen patients with active disease post-HCT.
View Article and Find Full Text PDFEngineered IL-21-Expressing Nanovesicles for Co-Delivery of GOX and Ferrocene to Induce Synergistic Anti-Tumor Effects.
Adv Healthc Mater
January 2025
School of Life Sciences, Anhui Medical University, Hefei, Anhui, 230032, China.
Glucose oxidase (GOX)-induced starvation is a safe treatment for tumor. However, the non-specific targeting of GOX and the plasticity of tumor metabolism lead to toxic side effects and low tumor mortality. Thus, it is necessary to develop a synergistic strategy with high tumor targeting specificity to enhance the mortality of GOX.
View Article and Find Full Text PDFEnhancement of anti-sarcoma immunity by NK cells engineered with mRNA for expression of a EphA2-targeted CAR.
Clin Transl Med
January 2025
Frazer Institute, Faculty of Medicine, The University of Queensland, Woolloongabba, Queensland, Australia.
Background: Paediatric sarcomas, including rhabdomyosarcoma, Ewing sarcoma and osteosarcoma, represent a group of malignancies that significantly contribute to cancer-related morbidity and mortality in children and young adults. These cancers share common challenges, including high rates of metastasis, recurrence or treatment resistance, leading to a 5-year survival rate of approximately 20% for patients with advanced disease stages. Despite the critical need, therapeutic advancements have been limited over the past three decades.
View Article and Find Full Text PDFIntegrative proteogenomic analyses provide novel interpretations of type 1 diabetes risk loci through circulating proteins.
Diabetes
January 2025
Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
Circulating proteins may be promising biomarkers or drug targets. Leveraging genome-wide association studies of type 1 diabetes (18,942 cases and 501,638 controls of European ancestry) and circulating protein abundances (10,708 European ancestry individuals), Mendelian randomization analyses were conducted to assess the associations between circulating abundances of 1,560 candidate proteins and the risk of type 1 diabetes, followed by multiple sensitivity and colocalization analyses, horizontal pleiotropy examinations, and replications. Bulk tissue and single-cell gene expression enrichment analyses were performed to explore candidate tissues and cell types for prioritized proteins.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!