ArticleJournal for immunotherapy of cancer2024
Engineered GM-CSF polarizes protumorigenic tumor-associated macrophages to an antitumorigenic phenotype and potently synergizes with IL-12 immunotherapy.
Article in Journal for immunotherapy of cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Applications of synthetic biology in biomedicine.Molecular biomedicine · 2026Review
- Innate Immune Cells in Non-Small Cell Lung Cancer: Roles in Tumor Progression and Therapeutic Responses.Cancer innovation · 2026Review
- DC-intrinsic SHP1 restrains central memory CD8⁺ T cell formation via the TCF-1/Wnt/β-Catenin axis.Medical oncology (Northwood, London, England) · 2026Article
- Article
- Nanoparticle Strategies for Bone Metastasis Immunotherapy: Targeting, Immune Reprogramming and Combination Therapy.Pharmaceutics · 2026Review
- Periostin in joint physiology and pathology: multiple roles from mechanisms to clinical perspectives.Histochemistry and cell biology · 2026Review
- An ontogeny-cytokine code determines macrophage response polarity and tumor outcomes.Communications biology · 2026Article
- T Cell Glycoengineering to Modulate Immune-Tumor Crosstalk: A Universal Non-Genetic Strategy for Enhanced Tumor Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Safety and immunologic impact of neoadjuvant/adjuvant GVAX, cyclophosphamide, pembrolizumab, and anti-CSF1R agent IMC-CS4 in pancreatic adenocarcinoma.Frontiers in immunology · 2026Article
- Rearming mesenchymal stem cells with engineering strategies to combat cancer.Frontiers in immunology · 2026Review
- Tumor-Associated Macrophages in Hepatocellular Carcinoma: From Ontogeny and Heterogeneity to Immune Evasion and Therapeutic Targeting.Journal of hepatocellular carcinoma · 2026Review
- CircFoxo3 knockdown inhibit gastric cancer progression by regulating Foxo3.In vitro cellular & developmental biology. Animal · 2026Article
- Histone lysine demethylases in breast cancer: molecular mechanisms, biological functions, and therapeutic intervention.Molecular cancer · 2025Review
- Oncolytic HSV-1 expressing GM-CSF and IL-12 enhances anti-tumor efficacy in immunocompetent murine melanoma model.Virologica Sinica · 2025Article
- Recombinant Oncolytic Viruses: Hexagonal Warriors in the Field of Solid Tumor Immunotherapy.Current issues in molecular biology · 2025Review
- Identification of prognostic genes related to T cell proliferation in papillary thyroid cancer based on single-cell RNA sequencing and bulk RNA sequencing data.Clinical and experimental medicine · 2025Article
- Igniting Cold Tumors: Multi-Omics-Driven Strategies to Overcome Immune Evasion and Restore Immune Surveillance.Oncology research · 2025Review
- Cancer vaccines: an update on recent achievements and prospects for cancer therapy.Clinical and experimental medicine · 2024Review
Corrections and comments
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Authors and funding
21 authors.
Funding
Abstract
backgroundThe use of immune checkpoint inhibitors (CPIs) has become a dominant regimen in modern cancer therapy, however immune resistance induced by tumor-associated macrophages (TAMs) with immune suppressive and evasion properties limits responses. Therefore, the rational design of immune modulators that can control the immune suppressive properties of TAMs and polarize them, as well as dendritic cells (DCs), toward a more proinflammatory phenotype is a principal objective in cancer immunotherapy.
methodsHere, using a protein engineering approach to enhance cytokine residence in the tumor microenvironment, we examined combined stimulation of the myeloid compartment via tumor stroma-binding granulocyte-macrophage colony-stimulating factor (GM-CSF) to enhance responses in both DCs and T cells via stroma-binding interleukin-12 (IL-12). We evaluated tumor responses at the levels of outcome, cellular responses, and cytokine responses in both the tumors and the tumor-draining lymph nodes. We further investigated the potentiation of DC response to IL-12 by GM-CSF stimulation ex vivo.
resultsEngineered GM-CSF restored an antitumorigenic tumor myeloid microenvironment otherwise suppressed by TAMs, while engineered IL-12 provided effector signals to T cells, thereby boosting both tumor-resident antitumor macrophage and CD8
conclusionOur strategy provides a rational design for combination immunotherapy targeting both myeloid and lymphoid compartments through complementary mechanisms.
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Registered trials
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