ArticleCancers2022
Reversing PD-1 Resistance in B16F10 Cells and Recovering Tumour Immunity Using a COX2 Inhibitor.
Article in Cancers, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 15 citations in OpenAlex.
- ANKRD11 deficiency reprograms CD8Nature immunology · 2026Article
- Cell membrane-encased thylakoid as white light triggered PDT therapy for facile and targeted choroidal melanoma treatment.Bioactive materials · 2026Article
- Adaptive resistance in cancer immunotherapy.Cellular & molecular immunology · 2026Review
- Targeting neutrophil-driven immunosuppression: A strategy to overcome immune checkpoint inhibitor resistance.Clinical and translational medicine · 2026Review
- Experimental Research Progress of mPGES-1 Inhibitor 2,5- dimethylcelecoxib in Various Diseases.Current medicinal chemistry · 2026Review
- Wnt3a-expressing cancer stem cells impair CD8Oncoimmunology · 2025Article
- COX-2 in lung cancer: Mechanisms, development, and targeted therapies.Chronic diseases and translational medicine · 2024Review
- Review
- Targeted demethylation and activation ofProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- Drug Repurposing to Circumvent Immune Checkpoint Inhibitor Resistance in Cancer Immunotherapy.Pharmaceutics · 2023Review
- Natural fulvic acids inhibit non-small-cell lung cancer through the COX-2/PGE2/EP4 axis: In silico and in vivo assessments.Heliyon · 2023Article
- Comedications with Immune Checkpoint Inhibitors: Involvement of the Microbiota, Impact on Efficacy and Practical Implications.Cancers · 2023Review
- Overview of Prostaglandin E2 (PGE2)-Targeting Radiolabelled Imaging Probes from Preclinical Perspective: Lessons Learned and Road Ahead.International journal of molecular sciences · 2023Review
- Transcriptomic and Proteomic Profiles for Elucidating Cisplatin Resistance in Head-and-Neck Squamous Cell Carcinoma.Cancers · 2022Article
- Targeting cancer-related inflammation with non-steroidal anti-inflammatory drugs: Perspectives in pharmacogenomics.Frontiers in pharmacology · 2022Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Immunotherapy is an effective method for tumour treatment. Anti-programmed cell death protein 1 (PD-1) and anti-programmed death-ligand 1 (PD-L1) monoclonal antibodies play a significant role in immunotherapy of most tumours; however, some patients develop drug resistance to PD-1/PD-L1 therapy. Cyclooxygenase-2 (COX2) is expressed in various solid tumours, and prostaglandin E2 (PGE2) drives the development of malignant tumours. We developed a drug-resistant B16F10 (B16F10-R) tumour mouse model through four rounds of selection in vivo. Subsequently, we investigated changes in PD-L1 expression and lymphocyte infiltration in B16F10-NR and B16F10-R tumours. Additionally, we explored the role of COX2 in acquired resistance to pembrolizumab, an anti-PD-1 treatment. Immune cell infiltration was significantly decreased in resistant tumours compared to B16F10-NR tumours; however, ptgs2 gene expression was significantly elevated in resistant tumours. Aspirin or celecoxib combined with pembrolizumab can effectively reverse tumour drug resistance. In addition, ptgs2 knockout or the use of the EP4 inhibitor E7046 abrogated drug resistance to anti-PD-1 treatment in B16F10-R tumour cells. Our study showed that inhibition of the COX2/PGE2/EP4 axis could increase the number of immune cells infiltrating the tumour microenvironment and recover drug-resistant tumour sensitivity to pembrolizumab. Thus, we highlight COX2 inhibition as a promising therapeutic target for drug-resistant tumours for future consideration.
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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.