Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Background: Solid tumors are characterized by a low blood supply, complex stromal architecture, and immunosuppressive milieu, which inhibit CAR-T cell entry and survival. CXCR5 has previously been employed to increase CAR-T cell infiltration into CXCL13+ cancers. On the other hand, IL-7 improves the survival and persistence of T cells inside a solid tumor milieu.
Methods: We constructed a novel NKG2D-based CAR (C5/IL7-CAR) that co-expressed CXCR5 and IL-7. The human osteosarcoma cell lines U-2 OS, 143B, and Mg63 highly expressed MICA/B and CXCL13, thus presenting a perfect avenue for the present study.
Results: Novel CAR-T cells are superior in their activation, degranulation, and cytokine release competence, hence lysing more target cells than conventional CAR. Furthermore, CXCR5 and IL-7 co-expression decreased the expression of PD-1, TIM-3, and TIGIT and increased Bcl-2 expression. Novel CAR-T cells show enhanced proliferation and differentiation towards the stem cell memory T cell phenotype. C5/IL7-CAR-T cells outperformed conventional CAR-T in eradicating osteosarcoma in mouse models and displayed better survival. Additionally, CXCR5 and IL-7 co-expression enhanced CAR-T cell numbers, cytokine release, and survival in implanted tumor tissues compared to conventional CAR-T cells. Mechanistically, C5/IL7-CAR-T cells displayed enhanced STAT5 signaling.
Conclusion: These findings highlight the potential of CXCR5 and IL-7 co-expression to improve CAR-T cell therapy efficacy against osteosarcoma.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11499113 | PMC |
| http://dx.doi.org/10.3389/fimmu.2024.1462076 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Tocilizumab and immune signatures for targeted management of cytokine release syndrome in immune checkpoint therapy.
Ann Oncol
April 2025
Centre Hospitalier Universitaire Vaudois (CHUV), Department of Medicine, Immunology and Allergy Service, University of Lausanne, Lausanne, Switzerland. Electronic address:
Article Synopsis
- The study identifies biomarkers that can differentiate between immune-related cytokine release syndrome (irCRS) and sepsis in oncology patients undergoing immune checkpoint inhibitor therapy.
- The analysis revealed that hepatocyte growth factor (HGF) and ferritin are particularly effective in predicting outcomes related to irHLH and Grade 3 irCRS, with a 100% positive and negative predictive value.
- Patients with severe irCRS who did not respond to corticosteroids showed complete resolution after treatment with tocilizumab (TCZ), highlighting the potential for targeted therapies in these cases.
Homeostatic signals, including IL-7 and self-MHC recognition, induce the development of peripheral helper T cells, which are enriched in the joints of rheumatoid arthritis.
J Transl Autoimmun
December 2024
Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Objective: Dysregulated T cell homeostasis has long been implicated in the pathogenesis of rheumatoid arthritis (RA), in the joint of which peripheral helper T (Tph) cells accumulate and form ectopic lymphoid organs. We examined whether homeostatic signals are involved in the development of Tph cells.
Methods: Human peripheral blood mononuclear cells were cultured with IL-7, the critical cytokine for T cell homeostasis.
A novel strategy of co-expressing CXCR5 and IL-7 enhances CAR-T cell effectiveness in osteosarcoma.
Front Immunol
October 2024
Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, China.
Background: Solid tumors are characterized by a low blood supply, complex stromal architecture, and immunosuppressive milieu, which inhibit CAR-T cell entry and survival. CXCR5 has previously been employed to increase CAR-T cell infiltration into CXCL13+ cancers. On the other hand, IL-7 improves the survival and persistence of T cells inside a solid tumor milieu.
View Article and Find Full Text PDFTh1/interferon-γ bias in 22q11.2 deletion syndrome is driven by memory T cells and exacerbated by IL-7.
Clin Immunol
November 2023
Department of Immunology, 2nd Faculty of Medicine, Charles University and University Hospital in Motol, Prague, Czech Republic. Electronic address:
Article Synopsis
- The study investigates how thymic dysplasia affects T cells in patients with 22q11.2 deletion syndrome, focusing on their characteristics and response to IL-7 treatment.
- Findings show a strong Th1 response in these patients, characterized by specific T cell expansions and increased production of various cytokines like IFN-γ and IL-10.
- IL-7 treatment leads to a reduction in naive T cells and an increase in exhaustion markers, indicating that the Th1 bias remains through adolescence and promotes early maturation of T cells.
Interleukin-21 in autoimmune and inflammatory skin diseases.
Eur J Immunol
April 2023
BIH Charité Clinician Scientist Program, Berlin Institute of Health at Charité-Universitätsmedizin Berlin, BIH Biomedical Innovation Academy, Berlin, Germany.
Studies on the role of interleukins (ILs) in autoimmune and inflammatory diseases allow for the better understanding of pathologic mechanisms of disease and reshaping of treatment modalities. The development of monoclonal antibodies targeting specific ILs or IL signaling pathways (i.e.
View Article and Find Full Text PDF