ArticleJournal for immunotherapy of cancer2020
Bone marrow MSC from pediatric patients with B-ALL highly immunosuppress T-cell responses but do not compromise CD19-CAR T-cell activity.
Article in Journal for immunotherapy of cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Mesenchymal Stromal Cells: Bridging the Gaps in Hematologic Disease Therapy.Stem cell reviews and reports · 2026Review
- Recent advances in CAR-MSCs: the new engine of cellular immunotherapy evolution.Journal of hematology & oncology · 2025Review
- Review
- The Bidirectional Interplay between T Cell-Based Immunotherapies and the Tumor Microenvironment.Cancer immunology research · 2025Review
- 3D Culture of MSCs for Clinical Application.Bioengineering (Basel, Switzerland) · 2024Review
- Pretreatment can alleviate programmed cell death in mesenchymal stem cells.World journal of stem cells · 2024Article
- Influence of Human Bone Marrow Mesenchymal Stem Cells Secretome from Acute Myeloid Leukemia Patients on the Proliferation and Death of K562 and K562-Lucena Leukemia Cell Lineages.International journal of molecular sciences · 2024Article
- Bone marrow-derived mesenchymal stromal cells obstruct AML-targeting CD8Cancer immunology, immunotherapy : CII · 2024Article
- Mesenchymal Stem Cell Transplantation in Type 1 Diabetes Treatment: Current Advances and Future Opportunity.Current stem cell research & therapy · 2024Review
- The role of MSCs and CAR-MSCs in cellular immunotherapy.Cell communication and signaling : CCS · 2023Review
- Characterization of mesenchymal stem cells in pre-B acute lymphoblastic leukemia.Frontiers in cell and developmental biology · 2023Article
- Engineering tandem CD33xCD146 CAR CIK (cytokine-induced killer) cells to target the acute myeloid leukemia niche.Frontiers in immunology · 2023Article
- Subclassification of B-acute lymphoblastic leukemia according to age, immunophenotype and microenvironment, predicts MRD risk in Mexican children from vulnerable regions.Frontiers in oncology · 2023Article
- Relapse after CAR-T cell therapy in B-cell malignancies: challenges and future approaches.Journal of Zhejiang University. Science. B · 2022Review
- Review
- Overcoming CAR-Mediated CD19 Downmodulation and Leukemia Relapse with T Lymphocytes Secreting Anti-CD19 T-cell Engagers.Cancer immunology research · 2022Article
- A novel and efficient tandem CD19- and CD22-directed CAR for B cell ALL.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Review
- Review
- Mesenchymal Stem Cell-Derived Exosomes and Their Potential Agents in Hematological Diseases.Oxidative medicine and cellular longevity · 2021Review
Corrections and comments
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAlthough adoptive transfer of CD19-directed chimeric antigen receptor (CAR) T-cells (CD19-CAR T-cells) achieves high rates of complete response in patients with B-cell acute lymphoblastic leukemia (B-ALL), relapse is common. Bone marrow (BM) mesenchymal stem/stromal cells (BM-MSC) are key components of the hematopoietic niche and are implicated in B-ALL pathogenesis and therapy resistance. MSC exert an immunosuppressive effect on T-cells; however, their impact on CD19-CAR T-cell activity is understudied.
methodsWe performed a detailed characterization of BM-MSC from pediatric patients with B-ALL (B-ALL BM-MSC), evaluated their immunomodulatory properties and their impact on CD19-CAR T-cell activity in vitro using microscopy, qRT-PCR, ELISA, flow cytometry analysis and in vivo using a preclinical model of severe colitis and a B-ALL xenograft model.
resultsWhile B-ALL BM-MSC were less proliferative than those from age-matched healthy donors (HD), the morphology, immunophenotype, differentiation potential and chemoprotection was very similar. Likewise, both BM-MSC populations were equally immunosuppressive in vitro and anti-inflammatory in an in vivo model of severe colitis. Interestingly, BM-MSC failed to impair CD19-CAR T-cell cytotoxicity or cytokine production in vitro using B-ALL cell lines and primary B-ALL cells. Finally, the growth of NALM6 cells was controlled in vivo by CD19-CAR T-cells irrespective of the absence/presence of BM-MSC.
conclusionsCollectively, our data demonstrate that pediatric B-ALL and HD BM-MSC equally immunosuppress T-cell responses but do not compromise CD19-CAR T-cell activity.
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