ArticleCancer science2014
Inhibition of mitogen-activated protein kinase pathway can induce upregulation of human leukocyte antigen class I without PD-L1-upregulation in contrast to interferon-γ treatment.
Article in Cancer science, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 32 citations in OpenAlex.
- Trial
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- Progress and prospects of the combination of BMI1-targeted therapy and immunotherapy in cervical cancer.American journal of cancer research · 2025Review
- PAK1 and Therapy Resistance in Melanoma.Cells · 2023Review
- PD-L1: expression regulation.Blood science (Baltimore, Md.) · 2023Review
- HLA class I antigen processing machinery defects in antitumor immunity and immunotherapy.Trends in cancer · 2021Review
- B2M gene expression shapes the immune landscape of lung adenocarcinoma and determines the response to immunotherapy.Immunology · 2021Article
- Landscape of EBV-positive gastric cancer.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2021Review
- Regulatory mechanisms of immune checkpoints PD-L1 and CTLA-4 in cancer.Journal of experimental & clinical cancer research : CR · 2021Review
- Combined inhibition of PD-1/PD-L1, Lag-3, and Tim-3 axes augments antitumor immunity in gastric cancer-T cell coculture models.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2021Article
- Regulation of PD-L1 expression in the tumor microenvironment.Journal of hematology & oncology · 2021Review
- A monocentric phase I study of vemurafenib plus cobimetinib plus PEG-interferon (VEMUPLINT) in advanced melanoma patients harboring the V600BRAF mutation.Journal of translational medicine · 2021Article
- Immune suppression caused by PD-L2 expression on tumor cells in gastric cancer.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2020Article
- Novel Biomarkers for Prediction of Response to Preoperative Systemic Therapies in Gastric Cancer.Journal of gastric cancer · 2019Review
- A subset of patients with MSS/MSI-low-colorectal cancer showed increased CD8(+) TILs together with up-regulated IFN-γ.Oncology letters · 2019Article
- MAPK pathway activity plays a key role in PD-L1 expression of lung adenocarcinoma cells.The Journal of pathology · 2019Article
- Phospho‑STAT1 expression as a potential biomarker for anti‑PD‑1/anti‑PD‑L1 immunotherapy for breast cancer.International journal of oncology · 2019Article
- A phase I/Ib study of OTSGC-A24 combined peptide vaccine in advanced gastric cancer.BMC cancer · 2018Article
- PD-L1 expression is mainly regulated by interferon gamma associated with JAK-STAT pathway in gastric cancer.Cancer science · 2018Article
- Upregulation of thioredoxin-1 in activated human NK cells confers increased tolerance to oxidative stress.Cancer immunology, immunotherapy : CII · 2017Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recently, we reported that human leukocyte antigen (HLA) class I expression is predominantly regulated by the mitogen-activated protein kinase (MAPK) pathway as one of the oncogenic regulations of HLA class I expression. In the present study, we examined mechanisms of how HLA class I and PD-L1 are regulated by MAPK inhibitors and interferon-γ (IFN-γ). Furthermore, we evaluated the expression of major signal transduction molecules by Western blot and anti-tumor CTL activity by a cytotoxic assay when HLA class I and PD-L1 were modulated by MAPK inhibitors and/or IFN-γ. As a result, we confirmed, as a more general phenomenon, that the inhibition of MAPK could upregulate HLA class I expression in a panel of human solid tumors (n = 26). Of note, we showed that MAPK inhibitors act on the upregulation of HLA class I expression through a different pathway from IFN-γ; there was an additive effect in the upregulation of HLA class I when treated with the combination of MAPK inhibitors and IFN-γ, and there was no overlapping activation of JAK2/STAT1 and Erk1/2 molecules when treated with either IFN-γ or MAPK inhibitors. Furthermore, we showed that IFN-γ-treatment impaired the tumor-specific CTL activity due to the upregulation of PD-L1 in spite of the upregulation of HLA class I, while MAPK inhibitors can augment the tumor-specific CTL activity due to the upregulated HLA class I without PD-L1 alterations. In conclusion, in addition to the original anti-proliferative activity, MAPK inhibitors may work toward the enhancement of T-cell-mediated anti-tumor immunity through the upregulation of HLA class I without the upregulation of PD-L1.
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