ArticlePloS one2015
An Autocrine Cytokine/JAK/STAT-Signaling Induces Kynurenine Synthesis in Multidrug Resistant Human Cancer Cells.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02967419 (The Study of the Relationship Between TWEAK/Fn14, JAK/STAT3 and IDO in the Immune Microenvironment of Endometrium in Repeated Implantation Failure), which is not on this map. Cited by 24 papers.
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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.
The Study of the Relationship Between TWEAK/Fn14, JAK/STAT3 and IDO in the Immune Microenvironment of Endometrium in Repeated Implantation Failure
Who cites it
24 citing papers in PubMed.
- Cancer IDO1-Mediated Tryptophan-Kynurenine Metabolic Reprogramming to Drive Skeletal Muscle Atrophy and Cachexia Acceleration.Journal of cachexia, sarcopenia and muscle · 2026Article
- T Cell Exhaustion in Cancer Immunotherapy: Heterogeneity, Mechanisms, and Therapeutic Opportunities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- A metabolic constraint in de novo NAD+ synthesis drives mucosal inflammation in IBD.Journal of Crohn's & colitis · 2026Article
- Integrated single cell and bulk RNA sequencing analyses reveal the impact of tryptophan metabolism on prognosis and immunotherapy in colon cancer.Scientific reports · 2025Article
- Therapeutic effect of three-dimensional hanging drop cultured human umbilical cord mesenchymal stem cells on osteoarthritis in rabbits.Stem cell research & therapy · 2024Article
- Bidirectional effects of the tryptophan metabolite indole-3-acetaldehyde on colorectal cancer.World journal of gastrointestinal oncology · 2024Article
- Beyond the barrier: the immune-inspired pathways of tumor extravasation.Cell communication and signaling : CCS · 2024Review
- IDO1-mediated kynurenine production inhibits IGFBP5 signaling to promote 5-fluorouracil-induced senescence escape and chemoresistance in colorectal cancer.American journal of cancer research · 2024Article
- A chemokine network of T cell exhaustion and metabolic reprogramming in renal cell carcinoma.Frontiers in immunology · 2023Article
- The AHR target gene scinderin activates the WNT pathway by facilitating the nuclear translocation of β-catenin.Journal of cell science · 2022Article
- Chemotherapeutic Resistance Genes of Breast Cancer Patients - An Overview.Advanced pharmaceutical bulletin · 2022Review
- Progress and challenges of multidrug resistance proteins in diseases.American journal of cancer research · 2022Review
- Structure-Activity Relationships of Triple-Action Platinum(IV) Prodrugs with Albumin-Binding Properties and Immunomodulating Ligands.Journal of medicinal chemistry · 2021Article
- Cisplatin Resistance and Redox-Metabolic Vulnerability: A Second Alteration.International journal of molecular sciences · 2021Review
- Emerging Landscapes of Tumor Immunity and Metabolism.Frontiers in oncology · 2020Review
- Signal transducer and activator of transcription (STAT)-5: an opportunity for drug development in oncohematology.Oncogene · 2019Review
- Rheumatoid Synovial Fluids Regulate the Immunomodulatory Potential of Adipose-Derived Mesenchymal Stem Cells Through a TNF/NF-κB-Dependent Mechanism.Frontiers in immunology · 2019Article
- Determinants of response and resistance to CD19 chimeric antigen receptor (CAR) T cell therapy of chronic lymphocytic leukemia.Nature medicine · 2018Article
- IL-13 Contributes to Drug Resistance of NK/T-Cell Lymphoma Cells by Regulating ABCC4.BioMed research international · 2018Article
- Unique proteome signature of post-chemotherapy ovarian cancer ascites-derived tumor cells.Scientific reports · 2016Article
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMultidrug resistant cancer cells are hard to eradicate for the inefficacy of conventional anticancer drugs. Besides escaping the cytotoxic effects of chemotherapy, they also bypass the pro-immunogenic effects induced by anticancer drugs: indeed they are not well recognized by host dendritic cells and do not elicit a durable anti-tumor immunity. It has not yet been investigated whether multidrug resistant cells have a different ability to induce immunosuppression than chemosensitive ones. We addressed this issue in human and murine chemosensitive and multidrug resistant cancer cells.
resultsWe found that the activity and expression of indoleamine 2,3-dioxygenase 1 (IDO1), which catalyzes the conversion of tryptophan into the immunosuppressive metabolite kynurenine, was higher in all the multidrug resistant cells analyzed and that IDO1 inhibition reduced the growth of drug-resistant tumors in immunocompetent animals. In chemoresistant cells the basal activity of JAK1/STAT1 and JAK1/STAT3 signaling was higher, the STAT3 inhibitor PIAS3 was down-regulated, and the autocrine production of STAT3-target and IDO1-inducers cytokines IL-6, IL-4, IL-1β, IL-13, TNF-α and CD40L, was increased. The disruption of the JAK/STAT signaling lowered the IDO1 activity and reversed the kynurenine-induced pro-immunosuppressive effects, as revealed by the restored proliferation of T-lymphocytes in STAT-silenced chemoresistant cells.
conclusionsOur work shows that multidrug resistant cells have a stronger immunosuppressive attitude than chemosensitive cells, due to the constitutive activation of the JAK/STAT/IDO1 axis, thus resulting chemo- and immune-evasive. Disrupting this axis may significantly improve the efficacy of chemo-immunotherapy protocols against resistant tumors.
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