ArticleIntegrative biology : quantitative biosciences from nano to macro2012
A quantitative systems approach to identify paracrine mechanisms that locally suppress immune response to Interleukin-12 in the B16 melanoma model.
Article in Integrative biology : quantitative biosciences from nano to macro, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Cell Communication Network factor 4 promotes tumor-induced immunosuppression in breast cancer.bioRxiv : the preprint server for biology · 2026Article
- Head-to-Head Comparison of CCN4, DNMT3A, PTPN11, and SPARC as Suppressors of Anti-tumor Immunity.Cellular and molecular bioengineering · 2023Article
- Cell Communication Network factor 4 promotes tumor-induced immunosuppression in melanoma.EMBO reports · 2022Article
- Signaling of Tumor-Derived sEV Impacts Melanoma Progression.International journal of molecular sciences · 2020Review
- Interleukin-12 elicits a non-canonical response in B16 melanoma cells to enhance survival.Cell communication and signaling : CCS · 2020Article
- Cell Communication Network Factor 4 (CCN4/WISP1) Shifts Melanoma Cells from a Fragile Proliferative State to a Resilient Metastatic State.Cellular and molecular bioengineering · 2020Article
- WNT1-inducible signaling pathway protein 1 (WISP1/CCN4) stimulates melanoma invasion and metastasis by promoting the epithelial-mesenchymal transition.The Journal of biological chemistry · 2019Article
- The emerging role of WISP proteins in tumorigenesis and cancer therapy.Journal of translational medicine · 2019Review
- The impact of human adipose tissue-derived stem cells on breast cancer cells: implications for cell-assisted lipotransfers in breast reconstruction.Stem cell research & therapy · 2017Article
- Melanoma exosomes deliver a complex biological payload that upregulates PTPN11 to suppress T lymphocyte function.Pigment cell & melanoma research · 2017Article
- Eavesdropping on altered cell-to-cell signaling in cancer by secretome profiling.Molecular & cellular oncology · 2016Article
- Interlocked positive and negative feedback network motifs regulate β-catenin activity in the adherens junction pathway.Molecular biology of the cell · 2015Article
- Exosomes: improved methods to characterize their morphology, RNA content, and surface protein biomarkers.The Analyst · 2015Article
- Enhancing the discovery and development of immunotherapies for cancer using quantitative and systems pharmacology: Interleukin-12 as a case study.Journal for immunotherapy of cancer · 2015Review
- Inferring alterations in cell-to-cell communication in HER2+ breast cancer using secretome profiling of three cell models.Biotechnology and bioengineering · 2014Article
- Alterations of gene expression and protein synthesis in co-cultured adipose tissue-derived stem cells and squamous cell-carcinoma cells: consequences for clinical applications.Stem cell research & therapy · 2014Article
- Induction of Wnt-inducible signaling protein-1 correlates with invasive breast cancer oncogenesis and reduced type 1 cell-mediated cytotoxic immunity: a retrospective study.PLoS computational biology · 2014Article
- An evolutionary perspective on anti-tumor immunity.Frontiers in oncology · 2012Article
- WISP1 is associated to advanced disease, EMT and an inflamed tumor microenvironment in multiple solid tumors.OncoimmunologyArticle
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Authors and funding
6 authors.
Funding
Abstract
Interleukin-12 (IL12) enhances anti-tumor immunity when delivered to the tumor microenvironment. However, local immunoregulatory elements dampen the efficacy of IL12. The identity of these local mechanisms used by tumors to suppress immunosurveillance represents a key knowledge gap for improving tumor immunotherapy. From a systems perspective, local suppression of anti-tumor immunity is a closed-loop system - where system response is determined by an unknown combination of external inputs and local cellular cross-talk. Here, we recreated this closed-loop system in vitro and combined quantitative high content assays, in silico model-based inference, and a proteomic workflow to identify the biochemical cues responsible for immunosuppression. Following an induction period, the B16 melanoma cell model, a transplantable model for spontaneous malignant melanoma, inhibited the response of a T helper cell model to IL12. This paracrine effect was not explained by induction of apoptosis or creation of a cytokine sink, despite both mechanisms present within the co-culture assay. Tumor-derived Wnt-inducible signaling protein-1 (WISP-1) was identified to exert paracrine action on immune cells by inhibiting their response to IL12. Moreover, WISP-1 was expressed in vivo following intradermal challenge with B16F10 cells and was inferred to be expressed at the tumor periphery. Collectively, the data suggest that (1) biochemical cues associated with epithelial-to-mesenchymal transition can shape anti-tumor immunity through paracrine action and (2) remnants of the immunoselective pressure associated with evolution in cancer include both sculpting of tumor antigens and expression of proteins that proactively shape anti-tumor immunity.
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