ArticleMolecular oncology2018
Inhibition of IL-6-JAK/Stat3 signaling in castration-resistant prostate cancer cells enhances the NK cell-mediated cytotoxicity via alteration of PD-L1/NKG2D ligand levels.
Article in Molecular oncology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers, 5 of them syntheses that pooled it.
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
87 citing papers in PubMed, 5 syntheses or guidelines pooled it, 130 citations in OpenAlex.
- 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
- 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
- Pooled 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
- Beyond suppression: the paradox of JAK inhibitors as amplifiers of cancer immunotherapy.Nature reviews. Immunology · 2026Review
- Molecular mechanisms and classification of castration-resistant prostate cancer: Insights into androgen receptor, cancer stem cells, and neuroendocrine features.Current urology · 2026Article
- Immune-tumor cell ligand-receptor axes driving metabolic reprogramming and therapeutic resistance in cancer.Frontiers in immunology · 2026Review
- Immunomodulatory properties of human dental pulp stromal cells: the role of IL-6/JAK/STAT3 pathway and PD-L1.Frontiers in immunology · 2026Article
- Therapeutic expansion of JAK inhibitors in Chinese dermatological practice: beyond atopic dermatitis to novel autoimmune frontiers.Frontiers in medicine · 2026Review
- PIM1 expression is prognostic in clear cell renal cell carcinoma and influenced by an IL-6/JAK/STAT axis.American journal of cancer research · 2026Article
- CAA-derived IL-6 promoted the PD-L1 expression of breast cancer via STAT3/miR-497a-5p signaling.Journal of cancer research and clinical oncology · 2025Article
- Inhibition of MCP1 (CCL2) Enhances Antitumor Activity of NK Cells Against HCC Cells Under Hypoxia.International journal of molecular sciences · 2025Article
- Immunohistochemical expression of PD-L1 in colorectal carcinoma among black patients and the clinicopathological correlates: a cross-sectional study.BMC gastroenterology · 2025Article
- The RNA binding protein CARHSP1 facilitates tumor growth, metastasis and immune escape by enhancing IL-17RA mRNA stabilization in prostate cancer.Cell & bioscience · 2025Article
- The role of immunotherapy and chemotherapy combinations in TKI-resistant EGFR-mutant non-small cell lung cancer: insights from real-world evidence.American journal of cancer research · 2025Article
- Exploring Natural Compounds Targeting PD-L1 and STAT3: Toxicogenomic Analysis, Virtual Screening, Molecular Docking, ADMET Evaluation, and Biological Activity Prediction.Current computer-aided drug design · 2025Article
- Advances in Interleukin-6 Family Cytokines and the Role in Respiratory Diseases.Journal of inflammation research · 2025Review
- Advances in the application of PD-1/PD-L1 immunotherapy for prostate cancer: a review.Frontiers in immunology · 2025Review
- Immunological features of EGFR-mutant non-small cell lung cancer and clinical practice: a narrative review.Journal of the National Cancer Center · 2024Review
27 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
10 authors at 3 institutions in 2 countries.
Funding
Abstract
To investigate whether IL-6 signaling affects the susceptibility of castration-resistant prostate cancer (CRPC) cells to cytotoxic action of natural killer (NK) cells, CRPC cell lines (having different IL-6 levels) were developed by lentiviral transduction. While observing no secreted IL-6 level in parental C4-2 and CWR22Rv1 cells, we found the IL-6 expression/secretion in these cells was induced after the transduction process and the IL-6 level difference in C4-2siIL-6/sc and CWR22siIL-6/sc cell CRPC cell sets could be detected. We then found that IL-6-knockdown cells were more susceptible to NK cell cytotoxicity than control cells due to lowered programmed death receptor ligand 1 (PD-L1) and increased NK group 2D (NKG2D) ligand levels. In animal studies, to concur with the in vitro results, we found that IL-6-expressing cell-derived tumors were more resistant to NK cell action than the tumors of IL-6-knockdown cells. Further, we discovered that JAK-Stat3 is the most critical IL-6 downstream signaling that modulates PD-L1/NKG2D ligand levels in CRPC cells. Furthermore, inhibition of the JAK or Stat3 signaling effectively increased the susceptibility of C4-2sc and CWRsc cells to NK cell cytotoxicity. We observed the most effective cytotoxicity when the PD-L1 Ab and JAK inhibitor (or Stat 3 inhibitor) were used together. These results suggest that the strategy of targeting IL-6 signaling (or its downstream signaling) may enhance the NK cell-mediated immune action to CRPC tumors, thus yielding clinical implications in developing future immunotherapeutics of exploiting this strategy to treat patients with CRPC.
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.