ArticleScientific reports2022
B-cell acute lymphoblastic leukemia promotes an immune suppressive microenvironment that can be overcome by IL-12.
Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- The role of chemokines and interleukins in acute lymphoblastic leukemia: a systematic review.Journal of applied biomedicine · 2024Pooled it
- Mining single-cell transcriptomic data reveals distinct T-cell population in pediatric B-ALL and AML at diagnosis.Blood advances · 2026Article
- Oleic Acid Integrated Acetalated Dextran Nanoparticles for Enhanced Chemotherapeutic Delivery to the Bone Marrow.ACS applied materials & interfaces · 2025Article
- Acquisition of an immunosuppressive microenvironment after anti-CD19 CAR T-cell therapy is associated with T-cell dysfunction and resistance.Journal for immunotherapy of cancer · 2025Article
- Identification of leukemia-enriched signature through the development of a comprehensive pediatric single-cell atlas.Nature communications · 2025Article
- The rewired immune microenvironment in leukemia.Nature immunology · 2025Review
- TIGIT/PVR axis regulates anti-tumor immunity in hematologic malignancies.Annals of hematology · 2025Review
- T cell exhaustion in pediatric B-ALL: current knowledge and future perspectives.Frontiers in immunology · 2025Review
- Inhibition of PNCK inflames tumor microenvironment and sensitizes head and neck squamous cell carcinoma to immune checkpoint inhibitors.Journal for immunotherapy of cancer · 2024Article
- Human Vγ9Vδ2 T cell expansion and their cytotoxic responses against cholangiocarcinoma.Scientific reports · 2024Article
- ID1 and ID3 functions in the modulation of the tumour immune microenvironment in adult patients with B-cell acute lymphoblastic leukaemia.Frontiers in immunology · 2024Article
- Siglec-15 Promotes Evasion of Adaptive Immunity in B-cell Acute Lymphoblastic Leukemia.Cancer research communications · 2023Article
- Multicolor Light-Induced Immune Activation via Polymer Photocaged Cytokines.Biomacromolecules · 2023Article
- AATF/Che-1 RNA polymerase II binding protein overexpression reduces the anti-tumor NK-cell cytotoxicity through activating receptors modulation.Frontiers in immunology · 2023Article
- Increased Expression of SRSF1 Predicts Poor Prognosis in Multiple Myeloma.Journal of oncology · 2023Article
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
Immunotherapies have revolutionized the treatment of B-cell acute lymphoblastic leukemia (B-ALL), but the duration of responses is still sub-optimal. We sought to identify mechanisms of immune suppression in B-ALL and strategies to overcome them. Plasma collected from children with B-ALL with measurable residual disease after induction chemotherapy showed differential cytokine expression, particularly IL-7, while single-cell RNA-sequencing revealed the expression of genes associated with immune exhaustion in immune cell subsets. We also found that the supernatant of leukemia cells suppressed T-cell function ex vivo. Modeling B-ALL in mice, we observed an altered tumor immune microenvironment, including compromised activation of T-cells and dendritic cells (DC). However, recombinant IL-12 (rIL-12) treatment of mice with B-ALL restored the levels of several pro-inflammatory cytokines and chemokines in the bone marrow and increased the number of splenic and bone marrow resident T-cells and DCs. RNA-sequencing of T-cells isolated from vehicle and rIL-12 treated mice with B-ALL revealed that the leukemia-induced increase in genes associated with exhaustion, including Lag3, Tigit, and Il10, was abrogated with rIL-12 treatment. In addition, the cytolytic capacity of T-cells co-cultured with B-ALL cells was enhanced when IL-12 and blinatumomab treatments were combined. Overall, these results demonstrate that the leukemia immune suppressive microenvironment can be restored with rIL-12 treatment which has direct therapeutic implications.
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