ArticleJournal for immunotherapy of cancer2023
Macrophage STING signaling promotes NK cell to suppress colorectal cancer liver metastasis via 4-1BBL/4-1BB co-stimulation.
Article in Journal for immunotherapy of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
77 citing papers in PubMed, 98 citations in OpenAlex.
- Next-generation macrophage engineering in cancer therapy: From TAM reprogramming to CAR-macrophages.Molecular therapy. Nucleic acids · 2026Review
- GPAT4 regulates antitumor immune response through activating the mtDNA-cGAS axis in cancer cells.Cell insight · 2026Article
- Gasdermin-Mediated Pyroptosis: Novel Strategies Against Colorectal Cancer.Cancer science · 2026Review
- The diversity of STING in regulating immune cell function and its role in liver diseases: from bench to bedside.Cell & bioscience · 2026Review
- The NLRP3 inflammasome as a dynamic context-dependent regulator: mechanisms, disease progression, and therapeutic implications.Journal of translational medicine · 2026Review
- Context-dependent actions of STING pathway in colitis and associated colon cancer.Genes & diseases · 2026Review
- Interactions Between Circulating Tumor Cells and the Immune System in Colorectal Cancer: Friends or Foes?Cancers · 2026Review
- PRKN mediates the ubiquitination of SCAF8 to reduce the mRNA stability of KLF5 and its transcriptional activation of EFNA3 in colorectal cancer.Cellular & molecular biology letters · 2026Article
- The role of the cGAS-STING pathway in male reproductive disorders.Molecular biology reports · 2026Review
- A Multi-Omics Framework Reveals Tumor Heterogeneity and Predicts Therapeutic Targets in Renal Cell Carcinoma.International journal of molecular sciences · 2026Article
- Extracellular cGAMP in health and disease.Molecular biomedicine · 2026Review
- Tumor microenvironment remodeling by STING agonism sensitizes endothelial cells to cytotoxic anti-PD-L1/L2 antibody.Journal of experimental & clinical cancer research : CR · 2026Article
- The dual roles of natural killer cells in liver immunity and tolerance: Implications for health and disease.Hepatology communications · 2026Review
- C5aR1 and cGAS/STING and their possible involvement in radiosensitivity of colorectal cancer.iScience · 2026Review
- Colorectal cancer pathogenesis, oncogenic signaling networks and targeted therapeutic advances.Molecular biomedicine · 2026Review
- Orosomucoid 2 promotes colorectal cancer liver metastasis by suppressing natural killer cell-mediated antitumor immunity by remodeling the serine and one-carbon metabolism pathway.Molecular cancer · 2026Article
- Key molecular mechanisms and regulatory networks in colorectal cancer liver metastasis.Biological procedures online · 2026Review
- Metabolic reprogramming in cancer: signaling pathways and therapeutic targets.Molecular cancer · 2026Review
- NLRPs and tumor: research progress from molecular mechanisms to clinical applications.Oncogene · 2026Review
- RNF216 as a Promising Biomarker for Prognosis, Immunotherapy, and Chemotherapy in LIHC: A Comprehensive Pan-Cancer Analysis and Experimental Validation.Journal of Cancer · 2026Article
17 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
aimsMacrophage innate immune response plays an important role in tumorigenesis. However, the role and mechanism of macrophage STING signaling in modulating tumor microenvironment to suppress tumor growth at secondary sites remains largely unclear.
methodsSTING expression was assessed in liver samples from patients with colorectal cancer (CRC) liver metastasis. Global or myeloid stimulator of interferon gene (STING)-deficient mice, myeloid NOD-like receptor protein 3 (NLRP3)-deficient mice, and wild-type (WT) mice were subjected to a mouse model of CRC liver metastasis by intrasplenic injection of murine colon carcinoma cells (MC38). Liver non-parenchymal cells including macrophages and natural killer (NK) cells were isolated for flow cytometry analysis. Bone marrow-derived macrophages pretreated with MC38 were co-cultured with splenic NK cells for in vitro studies.
resultsSignificant activation of STING signaling were detected in adjacent and tumor tissues and intrahepatic macrophages. Global or myeloid STING-deficient mice had exacerbated CRC liver metastasis and shorten survival, with decreased intrahepatic infiltration and impaired antitumor function of NK cells. Depletion of NK cells in WT animals increased their metastatic burden, while no significant effects were observed in myeloid STING-deficient mice. STING activation contributed to the secretion of interleukin (IL)-18 and IL-1β by macrophages, which optimized antitumor activity of NK cells by promoting the expression of 4-1BBL in macrophages and 4-1BB in NK cells, respectively. Moreover, MC38 treatment activated macrophage NLRP3 signaling, which was inhibited by STING depletion. Myeloid NLRP3 deficiency increased tumor burden and suppressed activation of NK cells. NLRP3 activation by its agonist effectively suppressed CRC liver metastasis in myeloid SITNG-deficient mice.
conclusionsWe demonstrated that STING signaling promoted NLRP3-mediated IL-18 and IL-1β production of macrophages to optimize the antitumor function of NK cells via the co-stimulation signaling of 4-1BBL/4-1BB.
Indexed as
Identifiers
What OpenQuestion holds
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.