ArticleBlood2023
Flotetuzumab and other T-cell immunotherapies upregulate MHC class II expression on acute myeloid leukemia cells.
Article in Blood, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 33 citations in OpenAlex.
- HSCs/MPPs as cells of origin with altered differentiation hierarchy impairing immunomicroenvironment inProceedings of the National Academy of Sciences of the United States of America · 2026Article
- TP53-mutated myelodysplastic syndromes and acute myeloid leukemia: a comprehensive overview of targeted approaches.Frontiers in oncology · 2026Review
- IL-1β-mediated suppression of CIITA attenuates IFN-γ-induced MHC-II expression on Fibroblasts.Cell communication and signaling : CCS · 2025Article
- Synergistic targeting strategies for prostate cancer.Nature reviews. Urology · 2025Review
- Decoding MHC loss: Molecular mechanisms and implications for immune resistance in cancer.Clinical and translational medicine · 2025Review
- CLEVER-1 targeting antibody, bexmarilimab, supports HLA-DR expression and alters ex vivo responsiveness to azacitidine and venetoclax in myeloid malignancies.Scientific reports · 2025Article
- Hypoxia impairs decitabine-induced expression of HLA-DR in acute myeloid leukaemia cell lines.Clinical epigenetics · 2025Article
- Advances in the application of patient-derived xenograft models in acute leukemia resistance.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Biology of post-transplant relapse: actionable features.Hematology. American Society of Hematology. Education Program · 2024Review
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- The Potential of Siglecs and Sialic Acids as Biomarkers and Therapeutic Targets in Tumor Immunotherapy.Cancers · 2024Review
- Impact of p53-associated acute myeloid leukemia hallmarks on metabolism and the immune environment.Frontiers in pharmacology · 2024Review
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- Unveiling novel insights in acute myeloid leukemia through single-cell RNA sequencing.Frontiers in oncology · 2024Review
- Lysosome-related genes predict acute myeloid leukemia prognosis and response to immunotherapy.Frontiers in immunology · 2024Article
- Metabolic instruction of the graft-versus-leukemia immunity.Frontiers in immunology · 2024Review
- Novel immunotherapies in the treatment of AML: is there hope?Hematology. American Society of Hematology. Education Program · 2023Article
- Relapse of acute myeloid leukemia after allogeneic stem cell transplantation: immune escape mechanisms and current implications for therapy.Molecular cancer · 2023Review
- Spatiotemporal evolution of AML immune microenvironment remodeling and RNF149-driven drug resistance through single-cell multidimensional analysis.Journal of translational medicine · 2023Article
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10 authors at 2 institutions in 1 country.
Funding
Abstract
Acute myeloid leukemia (AML) relapse is one of the most common and significant adverse events following allogeneic hematopoietic cell transplantation (HCT). Downregulation of major histocompatibility class II (MHC-II) surface expression on AML blasts may represent a mechanism of escape from the graft-versus-malignancy effect and facilitate relapse. We hypothesized that T-cell immunotherapies targeting AML antigens would upregulate MHC-II surface expression via localized release of interferon gamma (IFN-γ), a protein known to upregulate MHC-II expression via JAK-STAT signaling. We demonstrate that flotetuzumab (FLZ), a CD123 × CD3 bispecific DART molecule, and chimeric antigen receptor expressing T cells targeting CD123, CD33, or CD371 upregulate MHC-II surface expression in vitro on a THP-1 AML cell line with intermediate MHC-II expression and 4 primary AML samples from patients relapsing after HCT with low MHC-II expression. We additionally show that FLZ upregulates MHC-II expression in a patient-derived xenograft model and in patients with relapsed or refractory AML who were treated with FLZ in a clinical trial. Finally, we report that FLZ-induced MHC-II upregulation is mediated by IFN-γ. In conclusion, we provide evidence that T-cell immunotherapies targeting relapsed AML can kill AML via both MHC-independent mechanisms and by an MHC-dependent mechanism through local release of IFN-γ and subsequent upregulation of MHC-II expression.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.