ArticleClinical cancer research : an official journal of the American Association for Cancer Research2024
Multidimensional Immunotyping of Human NF1-Associated Peripheral Nerve Sheath Tumors Uncovers Tumor-Associated Macrophages as Key Drivers of Immune Evasion in the Tumor Microenvironment.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- SARC031: A Phase II Trial of Selumetinib and Sirolimus for Patients with Unresectable or Metastatic Malignant Peripheral Nerve Sheath Tumors (MPNST).Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Trial
- Review
- NF1 Leucine Rich Domain-Derived Extracellular Vesicles Remodel the Glioblastoma Immune Microenvironment via an ADAM17-Associated Inflammatory Program.Journal of extracellular vesicles · 2026Article
- DNA Hypomethylation Is Not Cell Intrinsically Toxic to Polycomb Repressive Complex 2 Deficient Malignant Peripheral Nerve Sheath Tumors.Genes, chromosomes & cancer · 2026Article
- Targeting CD3L1-NRP2 disarms myeloid-driven tumor immune evasion.EMBO molecular medicine · 2026Article
- Peripheral nerve sheath tumors-on-a-chip: Next-generation platforms for mechanistic and therapeutic studies.Materials today. Advances · 2026Article
- Immune landscape characterization of neurofibromas with atypical features in Neurofibromatosis1 reveals PD-1 and the Tim-3/Galectin-9 pathway as potential therapeutic targets.Acta neuropathologica communications · 2026Article
- Single-cell transcriptomic profiling of malignant peripheral nerve sheath tumors.Neuro-oncology advances · 2026Review
- Primary and acquired resistance to immunotherapy in NSCLC.Frontiers in immunology · 2026Review
- TRAP1 expression elicits pro-tumoral functions in macrophages associated to malignant peripheral nerve sheath tumor cells.Journal of experimental & clinical cancer research : CR · 2025Article
- Novel Therapeutics and the Path Toward Effective Immunotherapy in Malignant Peripheral Nerve Sheath Tumors.Cancers · 2025Review
- Single-cell tumor microenvironment profiling informs a circulating proteome test for the interception of malignant transformation in NF1 nerve sheath tumors.Research square · 2025Article
- DLK1 Distinguishes Subsets of NF1-Associated Malignant Peripheral Nerve Sheath Tumors with Divergent Molecular Signatures.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- A Critical Role of DC-SIGNImmunoTargets and therapy · 2025Article
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24 authors.
Funding
Abstract
purposeMalignant peripheral nerve sheath tumors (MPNST) are aggressive soft-tissue sarcomas and the leading cause of mortality in individuals with neurofibromatosis type 1 (NF1). Despite many clinical trials, outcomes for patients with MPNST have remained stagnant, and most succumb to their disease; thus, novel therapeutic approaches are needed. A better understanding of the MPNST immune ecosystem will aid in the development of strategies to activate the immune system against the tumor. In this study, we profile the tumor immune microenvironment (TIME) in NF1-associated peripheral nerve sheath tumors (PNST) to discover insights on the role played by tumor-infiltrating immune cells in malignant transformation. EXPERIMENTAL
designUsing fresh and formalin-fixed paraffin-embedded tissue from patients diagnosed with NF1-PNST, we dissected the TIME through IHC, multiparameter flow cytometry, and comparative transcriptomic studies.
resultsImmunophenotyping confirmed increased immune cell infiltration during malignant progression, with a predominance of infiltrating myeloid cells, particularly CD163+ tumor-associated macrophages (TAM). The T cells within MPNST exhibited signs of tumor activation, characterized by high programmed cell death 1 expression. Additionally, MPNST specimens demonstrated elevated levels of immunosuppressive TAM, with heightened PD-L1 expression. The proportion of CD163+ myeloid cells within the TIME correlated with poorer progression-free survival. Notably, loss of H3K27 trimethylation correlated with low immune cell infiltration in MPNST.
conclusionsMalignant transformation of NF1-PNST is characterized by an immunosuppressive microenvironment comprising TAM with high expression of PD-L1, which is associated with inferior outcomes. These findings suggest the clinical potential of immune-modulating therapeutics that can unleash an antitumor immune response.
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