ArticleMolecular medicine reports2018
Combined inhibition of JAK1,2/Stat3‑PD‑L1 signaling pathway suppresses the immune escape of castration‑resistant prostate cancer to NK cells in hypoxia.
Article in Molecular medicine reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 5 of them syntheses that pooled it.
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40 citing papers in PubMed, 5 syntheses or guidelines pooled it, 51 citations in OpenAlex.
- What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 3: PD-L1, Intracellular Signaling Pathways and Tumor Microenvironment.International journal of molecular sciences · 2021Pooled it
- What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 5: Epigenetic Regulation of PD-L1.International journal of molecular sciences · 2021Pooled it
- Pooled it
- What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 4: Experimental Treatments in Pre-Clinical Studies (Cell Lines and Mouse Models).International journal of molecular sciences · 2021Pooled it
- Pooled it
- Structure-guided discovery of a dual JAK2/RAGE modulator reveals a computationally driven strategy for targeting convergent oncogenic signaling in renal cell carcinoma.Journal of computer-aided molecular design · 2026Article
- Human Group IIA Secreted Phospholipase AInternational journal of molecular sciences · 2026Review
- Adaptive therapy for perioperative non-small cell lung cancer: strategies guided by dynamic minimal residual disease adjustment.Translational oncology · 2026Review
- STAT3 at the tumor-immune interface: mechanisms of immune escape and therapeutic opportunities.Frontiers in immunology · 2026Review
- Adaptation of Natural Killer Cells to Hypoxia: A Review of the Transcriptional, Translational, and Metabolic Processes.ImmunoTargets and therapy · 2025Review
- Hypoxic tumor microenvironment: Destroyer of natural killer cell function.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2024Article
- Advances in metabolic reprogramming of NK cells in the tumor microenvironment on the impact of NK therapy.Journal of translational medicine · 2024Review
- Transcriptome analysis of anaerobic glycolysis effects on Jurkat T cell proliferation.Central-European journal of immunology · 2024Article
- Article
- Functional crosstalk and regulation of natural killer cells in tumor microenvironment: Significance and potential therapeutic strategies.Genes & diseases · 2023Review
- HIF1α-dependent and independent pathways regulate the expression of PD-L1 in prostate cancer.Medical oncology (Northwood, London, England) · 2023Article
- PD-L1: expression regulation.Blood science (Baltimore, Md.) · 2023Review
- Comprehensive pan-cancer analysis of STAT3 as a prognostic and immunological biomarker.Scientific reports · 2023Article
- Addressing Natural Killer Cell Dysfunction and Plasticity in Cell-Based Cancer Therapeutics.Cancers · 2023Review
- Intratumoral immune heterogeneity of prostate cancer characterized by typing and hub genes.Journal of cellular and molecular medicine · 2023Article
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Castration‑resistant prostate cancer (CRPC) is difficult to treat in current clinical practice. Hypoxia is an important feature of the CRPC microenvironment and is closely associated with the progress of CRPC invasion. However, no research has been performed on the immune escape of CRPC from NK cells. The present study focused on this subject. Firstly, when the CRPC cell lines C4‑2 and CWR22Rv1 were induced by hypoxia, the expression of the UL16 binding protein (ULBP) ligand family of natural killer (NK) group 2D (NKG2D; ULBP‑1, ULBP‑2 and ULBP‑3) and MHC class I chain‑related proteins A and B (MICA/MICB) decreased. NKG2D is the main activating receptor of NK cells. Tumor cells were then co‑cultured with NK cells to conduct NK cell‑mediated cytotoxicity experiments, which revealed the decreased immune cytolytic activity of NK cells on hypoxia‑induced CRPC cells. In exploring the mechanism behind this observation, an increase in programmed death‑ligand 1 (PD‑L1) expression in CRPC cells induced by hypoxia was observed, while the addition of PD‑L1 antibody effectively reversed the expression of NKG2D ligand and enhanced the cytotoxic effect of NK cells on CRPC cells. In the process of exploring the upstream regulatory factors of PD‑L1, inhibition of the Janus kinase (JAK)1,2/signal transducer and activator of transcription 3 (Stat3) signaling pathway decreased the expression of PD‑L1 in CRPC cells. Finally, it was observed that combined inhibition of JAK1,2/PD‑L1 or Stat3/PD‑L1 was more effective than inhibition of a single pathway in enhancing the immune cytolytic activity of NK cells. Taking these results together, it is thought that combined inhibition of the JAK1,2/PD‑L1 and Stat3/PD‑L1 signaling pathways may enhance the immune cytolytic activity of NK cells toward hypoxia‑induced CRPC cells, which is expected to provide novel ideas and targets for the immunotherapy of CRPC.
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