ArticleOncotarget2016
Activation of the PD-1/PD-L1 immune checkpoint confers tumor cell chemoresistance associated with increased metastasis.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers, 6 of them syntheses that pooled it.
What it found
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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
101 citing papers in PubMed, 6 syntheses or guidelines pooled it, 181 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
- 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
- Immunotherapy as a Promising Treatment for Prostate Cancer: A Systematic Review.Journal of immunology research · 2017Pooled it
- Single-center phase 2 study of PD-1 inhibitor combined with DNA hypomethylation agent + CAG regimen in patients with relapsed/refractory acute myeloid leukemia.Cancer immunology, immunotherapy : CII · 2023Trial
- Elevated serum soluble programmed cell death ligand 1 concentration as a potential marker for poor prognosis in small cell lung cancer patients with chemotherapy.Respiratory research · 2018Trial
- PD-L1 in Ovarian Cancer: Immune Evasion, Tumor-Intrinsic Signaling, and Chemoresistance.Cancer medicine · 2026Review
- PD-L1-positive circulating tumor cells associate with tumor malignancy and impaired circulating immunity in patients with gastrointestinal tumors.Scientific reports · 2026Article
- Navigating chemoresistance in triple-negative breast cancer: interplay between molecular signalling pathways and immune microenvironment.Molecular biology reports · 2026Review
- Bioactive Natural Compounds in Triple-Negative Breast Cancer: Molecular Targets and Therapeutic Perspectives.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Genetically bio-engineered PD-L1 targeted exosomes for immunotherapy of resistant triple negative breast cancer.Drug delivery and translational research · 2026Article
- Dual role of IFNγ in reprogramming the undifferentiated pleomorphic sarcoma cell line JBT19 towards cytotoxic chemotherapy and antitumor immunity.Oncology letters · 2026Article
- Tumor-Intrinsic PD-1 Regulatory Network Drives Lapatinib Resistance in HER2⁺ Breast Cancer: An Integrative Bioinformatics Analysis.Asian Pacific journal of cancer prevention : APJCP · 2026Article
- Anti-CSF-1R therapy with combined immuno-chemotherapy coordinate an adaptive immune response to eliminate macrophage enriched triple negative breast cancers.Nature communications · 2026Article
- Kinome-Wide Screening Identifies FAK as a Novel Post-Translational Regulator of PD-L1 Stability and Immune Evasion in Triple-Negative Breast Cancer.International journal of molecular sciences · 2025Article
- PD-1/PD-L1 Inhibitors and Chemotherapy Synergy: Impact on Drug Resistance and PD-L1 Expression in Breast Cancer-Immune Cell Co-Cultures.International journal of molecular sciences · 2025Article
- Enhanced antitumor efficacy of bispecific antibody blocking PD-L1 and LAG-3 with doxorubicin: mechanism and safety evaluation.Breast cancer research and treatment · 2025Article
- Impact of Doxorubicin and Docetaxel on Immune Checkpoint Expression in Colorectal Cancer: Insights into Chemotherapy Resistance Mechanisms.Biochemical genetics · 2025Article
41 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 2 institutions in 2 countries.
Funding
Abstract
The ability of tumor cells to avoid immune destruction (immune escape) as well as their acquired resistance to anti-cancer drugs constitute important barriers to the successful management of cancer. Interaction between the Programmed Death Ligand 1 (PD-L1) on the surface of tumor cells with the Programmed Death-1 (PD-1) receptor on cytotoxic T lymphocytes leads to inactivation of these immune effectors and, consequently, immune escape. Here we show that the PD-1/PD-L1 axis also leads to tumor cell resistance to conventional chemotherapeutic agents. Using a panel of PD-L1-expressing human and mouse breast and prostate cancer cell lines, we found that incubation of breast and prostate cancer cells in the presence of purified recombinant PD-1 resulted in resistance to doxorubicin and docetaxel as determined using clonogenic survival assays. Co-culture with PD-1-expressing Jurkat T cells also promoted chemoresistance and this was prevented by antibody blockade of either PD-L1 or PD-1 or by silencing of the PD-L1 gene. Moreover, inhibition of the PD-1/PD-L1 axis using anti-PD-1 antibody enhanced doxorubicin chemotherapy to inhibit metastasis in a syngeneic mammary orthotopic mouse model of metastatic breast cancer. To further investigate the mechanism of tumor cell survival advantage upon PD-L1 ligation, we show that exposure to rPD-1 promoted ERK and mTOR growth and survival pathways leading to increased cell proliferation. Overall, the findings of this study indicate that combinations of chemotherapy and immune checkpoint blockade may limit chemoresistance and progression to metastatic disease.
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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.