ArticleProceedings of the National Academy of Sciences of the United States of America2020
Targeting a scavenger receptor on tumor-associated macrophages activates tumor cell killing by natural killer cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers.
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Who cites it
115 citing papers in PubMed, 169 citations in OpenAlex.
- Trial
- A tumor-on-a-chip model reveals and targets reciprocal macrophage-NK cell crosstalk to advance immunotherapy screening.Microsystems & nanoengineering · 2026Article
- Cancer immunotherapy targeting murine myeloid cells requires endosomal pattern recognition.Nature communications · 2026Article
- Targeting macrophage-driven NK cell immunosuppression to improve cancer immunotherapy.Journal for immunotherapy of cancer · 2026Review
- MARCO promotes cholangiocarcinogenesis by inducing immunosuppression and its targeting reduces tumor growth.Signal transduction and targeted therapy · 2026Article
- Imaging-guided optimization of biodistribution and antitumor efficacy of L19-based immunocytokines.Translational oncology · 2026Article
- Identification and characterization of MARCO-expressing tumor-associated macrophages in pancreatic ductal adenocarcinoma with pan-cancer relevance.NPJ precision oncology · 2026Article
- scSurv: a deep generative model for single-cell survival analysis.Bioinformatics (Oxford, England) · 2026Article
- Article
- Harnessing the Power of CAR-NK Cells for Solid Tumors: Challenges, Innovations, and Future Frontiers in Immunotherapy.Cancer communications (London, England) · 2026Review
- Spatial transcriptomics and histopathological analyses reveal potential biomarkers and immune features linked to recurrence in head and neck cancer.Frontiers in immunology · 2026Article
- Nocardia rubra cell wall skeleton-induced MARCO expression: implications for improved phagocytosis and cytokine secretion in tumor-associated macrophages.Frontiers in immunology · 2026Article
- Macrophage reprogramming through scavenger receptor-guided and cathepsin B-triggered nanodelivery: from intracellular mechanisms to translational applications.Frontiers in immunology · 2026Review
- Class A scavenger receptor MARCO negatively regulates Ace expression and aldosterone production.eLife · 2025Article
- Article
- Review
- Immunometabolic reprogramming in lung cancer: interplay between immune and stem-like cells in immune checkpoint inhibitor resistance.Journal of translational medicine · 2025Review
- CAR NK cell therapy for solid tumors: potential and challenges.Antibody therapeutics · 2025Review
- Understanding the complexity of tumor-associated macrophages: Druggable and therapeutic insights.Acta pharmaceutica Sinica. B · 2025Review
- Article
55 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 2 institutions in 2 countries.
Funding
Abstract
Tumor-associated macrophages (TAMs) can have protumor properties, including suppressing immune responses, promoting vascularization and, consequently, augmenting tumor progression. To stop TAM-mediated immunosuppression, we use a novel treatment by injecting antibodies specific for scavenger receptor MARCO, which is expressed on a specific subpopulation of TAMs in the tumor. We now report the location of this TAM as well as the pleiotropic mechanism of action of anti-MARCO antibody treatment on tumor progression and further show that this is potentially relevant to humans. Using specific targeting, we observed decreased tumor vascularization, a switch in the metabolic program of MARCO-expressing macrophages, and activation of natural killer (NK) cell killing through TNF-related apoptosis-inducing ligand (TRAIL). This latter activity reverses the effect of melanoma cell-conditioned macrophages in blocking NK activation and synergizes with T cell-directed immunotherapy, such as antibodies to PD-1 or PD-L1, to enhance tumor killing. Our study thus reveals an approach to targeting the immunosuppressive tumor microenvironment with monoclonal antibodies to enhance NK cell activation and NK cell-mediated killing. This can complement existing T cell-directed immunotherapy, providing a promising approach to combinatorial immunotherapy for cancer.
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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.