ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2021
Interleukin-33 is a Novel Immunosuppressor that Protects Cancer Cells from TIL Killing by a Macrophage-Mediated Shedding Mechanism.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 34 citations in OpenAlex.
- Clinicopathological and molecular characterization of tumor-associated macrophages in sporadic and Xeroderma Pigmentosum-related cutaneous melanoma.BMC cancer · 2026Article
- Targeting NKG2D/NKG2DL axis in cancer immunotherapy: mechanisms and therapeutic applications.Journal of translational medicine · 2026Review
- The role of matrix metalloproteinase 9 in immune-mediated skin diseases.Frontiers in immunology · 2026Review
- Unlocking IL-33: New Insights into Tumor Immunity.Immune network · 2025Review
- Article
- Clinical and Fundamental Research Progressions on Tumor-Infiltrating Lymphocytes Therapy in Cancer.Vaccines · 2025Review
- Identification of a Novel Small Molecule STING Agonist Reshaping the Immunomicroenvironment of Pancreatic Ductal Adenocarcinoma.International journal of biological sciences · 2025Article
- The multifaceted role of the stroma in the healthy prostate and prostate cancer.Journal of translational medicine · 2024Review
- Alarmins in cutaneous malignant melanoma: An updated overview of emerging evidence on their pathogenetic, diagnostic, prognostic, and therapeutic role.The Journal of dermatology · 2024Review
- EBV promotes TCR-T-cell therapy resistance by inducing CD163+M2 macrophage polarization and MMP9 secretion.Journal for immunotherapy of cancer · 2024Article
- Article
- Targeting the lipid metabolic reprogramming of tumor-associated macrophages: A novel insight into cancer immunotherapy.Cellular oncology (Dordrecht, Netherlands) · 2024Review
- Revolutionizing cancer treatment: the emerging potential and potential challenges ofTheranostics · 2024Review
- Tumor-produced immune regulatory factors as a therapeutic target in cancer treatment.Frontiers in immunology · 2024Review
- Review
- Biomimetic nanoparticles drive the mechanism understanding of shear-wave elasticity stiffness in triple negative breast cancers to predict clinical treatment.Bioactive materials · 2023Article
- Article
- Prognostic Profiling of the EMT-Associated and Immunity-Related LncRNAs in Lung Squamous Cell Carcinomas.Cells · 2022Article
- Roles for macrophage-polarizing interleukins in cancer immunity and immunotherapy.Cellular oncology (Dordrecht, Netherlands) · 2022Review
- Neuroendocrine Regulation of Stress-Induced T Cell Dysfunction during Lung Cancer Immunosurveillance via the Kisspeptin/GPR54 Signaling Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
Corrections and comments
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Authors and funding
19 authors at 7 institutions in 3 countries.
Funding
Abstract
Recognition of specific antigens expressed in cancer cells is the initial process of cytolytic T cell-mediated cancer killing. However, this process can be affected by other non-cancerous cellular components in the tumor microenvironment. Here, it is shown that interleukin-33 (IL-33)-activated macrophages protect melanoma cells from tumor-infiltrating lymphocyte-mediated killing. Mechanistically, IL-33 markedly upregulates metalloprotease 9 (MMP-9) expression in macrophages, which acts as a sheddase to trim NKG2D, an activating receptor expressed on the surface of natural killer (NK) cells, CD8+ T cells, subsets of CD4+ T cells, iNKT cells, and γδ T cells. Further, MMP-9 also cleaves the MHC class I molecule, cell surface antigen-presenting complex molecules, expressed in melanoma cells. Consequently, IL-33-induced macrophage MMP-9 robustly mitigates the tumor killing-effect by T cells. Genetic and pharmacological loss-of-function of MMP-9 sheddase restore T cell-mediated cancer killing. Together, these data provide compelling in vitro and in vivo evidence showing novel mechanisms underlying the IL-33-macrophage-MMP-9 axis-mediated immune tolerance against cancer cells. Targeting each of these signaling components, including IL-33 and MMP-9 provides a new therapeutic paradigm for improving anticancer efficacy by immune therapy.
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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.