ArticleJournal of hepatology2024
IL-10 dampens antitumor immunity and promotes liver metastasis via PD-L1 induction.
Article in Journal of hepatology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers.
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101 citing papers in PubMed, 114 citations in OpenAlex.
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- GABRD promotes hepatocellular carcinoma progression via the IL-10RA/JAK2-STAT3 signaling axis.Cell death & disease · 2026Article
- Extracellular vesicles from chemotherapy-induced senescent tumor cells reprogram hepatic phospholipid metabolism to promote pancreatic cancer liver metastasis.Journal of experimental & clinical cancer research : CR · 2026Article
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- SpatialQuery: scalable discovery and molecular characterization of multicellular motifs from spatial omics data.bioRxiv : the preprint server for biology · 2026Article
- [Research progress on poor response, resistance mechanisms, and influencing factors of immunotherapy for hepatocellular carcinoma].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026Review
- Potential role of leptin in colorectal cancer liver metastasis involving lipid metabolic reprogramming and immunosuppressive macrophage polarization.Scientific reports · 2026Article
- The Molecular Signature of Early-Onset Colorectal Cancer Liver Metastases: Distinct Biology and Clinical Challenges.International journal of molecular sciences · 2026Review
- IL-15 promotes immune escape, invasion, and metastasis of pancreatic cancer by upregulating PD-L1 expression via the JAK1/STAT1/IRF1 pathway.Cell communication and signaling : CCS · 2026Article
- Dual regulation of CXCR6Journal for immunotherapy of cancer · 2026Article
- IL-8 positive cancer-associated fibroblasts drive breast cancer progression and immune evasion: insights from GWAS and single-cell transcriptomics.BMC cancer · 2026Article
- mRNA vaccines in cancer immunotherapy: current progress and perspectives in solid tumors and hematologic malignancies.MedScience · 2026Review
41 more citing papers are in PubMed but not listed here.
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Authors and funding
37 authors at 5 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND &
aimsThe liver is one of the organs most commonly affected by metastasis. The presence of liver metastases has been reported to be responsible for an immunosuppressive microenvironment and diminished immunotherapy efficacy. Herein, we aimed to investigate the role of IL-10 in liver metastasis and to determine how its modulation could affect the efficacy of immunotherapy in vivo.
methodsTo induce spontaneous or forced liver metastasis in mice, murine cancer cells (MC38) or colon tumor organoids were injected into the cecum or the spleen, respectively. Mice with complete and cell type-specific deletion of IL-10 and IL-10 receptor alpha were used to identify the source and the target of IL-10 during metastasis formation. Programmed death ligand 1 (PD-L1)-deficient mice were used to test the role of this checkpoint. Flow cytometry was applied to characterize the regulation of PD-L1 by IL-10.
resultsWe found that Il10-deficient mice and mice treated with IL-10 receptor alpha antibodies were protected against liver metastasis formation. Furthermore, by using IL-10 reporter mice, we demonstrated that Foxp3+ regulatory T cells (Tregs) were the major cellular source of IL-10 in liver metastatic sites. Accordingly, deletion of IL-10 in Tregs, but not in myeloid cells, led to reduced liver metastasis. Mechanistically, IL-10 acted on Tregs in an autocrine manner, thereby further amplifying IL-10 production. Furthermore, IL-10 acted on myeloid cells, i.e. monocytes, and induced the upregulation of the immune checkpoint protein PD-L1. Finally, the PD-L1/PD-1 axis attenuated CD8-dependent cytotoxicity against metastatic lesions.
conclusionsTreg-derived IL-10 upregulates PD-L1 expression in monocytes, which in turn reduces CD8+ T-cell infiltration and related antitumor immunity in the context of colorectal cancer-derived liver metastases. These findings provide the basis for future monitoring and targeting of IL-10 in colorectal cancer-derived liver metastases. IMPACT AND IMPLICATIONS: Liver metastasis diminishes the effectiveness of immunotherapy and increases the mortality rate in patients with colorectal cancer. We investigated the role of IL-10 in liver metastasis formation and assessed its impact on the effectiveness of immunotherapy. Our data show that IL-10 is a pro-metastatic factor involved in liver metastasis formation and that it acts as a regulator of PD-L1. This provides the basis for future monitoring and targeting of IL-10 in colorectal cancer-derived liver metastasis.
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