ArticleCancers2020
Pemetrexed Enhances Membrane PD-L1 Expression and Potentiates T Cell-Mediated Cytotoxicity by Anti-PD-L1 Antibody Therapy in Non-Small-Cell Lung Cancer.
Article in Cancers, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 25 papers, 1 of them a synthesis 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
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- An Indirect Comparison Between Nivolumab + Ipilimumab + Two Cycles of Chemotherapy vs. Pembrolizumab + Chemotherapy as First-Line Treatment for Metastatic Non-Small Cell Lung Cancer.Frontiers in oncology · 2021Pooled it
- PI3K/AKT/mTOR signaling at the immune checkpoint interface in lung cancer: molecular mechanisms, Tumor-Immune remodeling, therapeutic resistance, and emerging treatment strategies.Frontiers in cell and developmental biology · 2026Review
- Bi-directional metabolic reprogramming between cancer cells and T cells reshapes the anti-tumor immune response.PLoS biology · 2025Article
- Comparative Survival Analysis of Anti-Angiogenic Agent Plus Immunochemotherapy in NSCLC Patients After Frontline EGFR-TKI Treatment: A Retrospective Cohort Study.The Kaohsiung journal of medical sciences · 2025Article
- PD-L1 pfeRNAs as blood-based predictors of treatment response of unresectable malignant pleural mesothelioma patients administered Durvalumab with cisplatin and pemetrexed as first-line therapy.Non-coding RNA research · 2025Article
- Article
- Safety and efficacy of neoadjuvant therapy with tislelizumab plus chemotherapy for locally advanced head and neck squamous cell carcinoma: a single-arm, retrospective study.Cancer immunology, immunotherapy : CII · 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
- Case Report: Abscopal effect and long-term survival in a PD-L1 negative NSCLC patient treated with radiotherapy and immuno-chemotherapy.Frontiers in immunology · 2025Article
- Enhancing Effector Jurkat Cell Activity and Increasing Cytotoxicity against A549 Cells Using Nivolumab as an Anti-PD-1 Agent Loaded on Gelatin Nanoparticles.Gels (Basel, Switzerland) · 2024Article
- Inhalable metal-organic framework-mediated cuproptosis combined with PD-L1 checkpoint blockade for lung metastasis synergistic immunotherapy.Acta pharmaceutica Sinica. B · 2024Article
- Article
- Pemetrexed combined with dual immune checkpoint blockade enhances cytotoxic T lymphocytes against lung cancer.Cancer science · 2023Article
- Exploring the Molecular Players behind the Potentiation of Chemotherapy Effects by Durvalumab in Lung Adenocarcinoma Cell Lines.Pharmaceutics · 2023Article
- Soluble PD-L1: a potential dynamic predictive biomarker for immunotherapy in patients with proficient mismatch repair colorectal cancer.Journal of translational medicine · 2023Article
- Schedule-Dependent Treatment Increases Chemotherapy Efficacy in Malignant Pleural Mesothelioma.International journal of molecular sciences · 2022Article
- The generation of PD-L1 and PD-L2 in cancer cells: From nuclear chromatin reorganization to extracellular presentation.Acta pharmaceutica Sinica. B · 2022Review
- KRAS G12 isoforms exert influence over up-front treatments: A retrospective, multicenter, Italian analysis of the impact of first-line immune checkpoint inhibitors in an NSCLC real-life population.Frontiers in oncology · 2022Article
- Dramatic response to immunotherapy in an epidermal growth factor receptor-mutant non-small cell lung cancer: A case report.World journal of clinical cases · 2021Article
- Multicellular Effects of STAT3 in Non-small Cell Lung Cancer: Mechanistic Insights and Therapeutic Opportunities.Cancers · 2021Review
Corrections and comments
- Erratum issued
Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
Immunotherapy has significantly changed the treatment landscape for advanced non-small-cell lung cancer (NSCLC) with the introduction of drugs targeting programmed cell death protein-1 (PD-1) and programmed cell death ligand-1 (PD-L1). In particular, the addition of the anti-PD-1 antibody pembrolizumab to platinum-pemetrexed chemotherapy resulted in a significantly improved overall survival in patients with non-squamous NSCLC, regardless of PD-L1 expression. In this preclinical study, we investigated whether chemotherapy can modulate PD-L1 expression in non-squamous NSCLC cell lines, thus potentially affecting immunotherapy efficacy. Among different chemotherapeutic agents tested, only pemetrexed increased PD-L1 levels by activating both mTOR/P70S6K and STAT3 pathways. Moreover, it also induced the secretion of cytokines, such as IFN-γ and IL-2, by activated peripheral blood mononuclear cells PBMCs that further stimulated the expression of PD-L1 on tumor cells, as demonstrated in a co-culture system. The anti-PD-1/PD-L1 therapy enhanced T cell-mediated cytotoxicity of NSCLC cells treated with pemetrexed and expressing high levels of PD-L1 in comparison with untreated cells. These data may explain the positive results obtained with pemetrexed-based chemotherapy combined with pembrolizumab in PD-L1-negative NSCLC and can support pemetrexed as one of the preferable chemotherapy partners for immunochemotherapy combination regimens.
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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.