ArticleJournal for immunotherapy of cancer2020
Antimetabolite pemetrexed primes a favorable tumor microenvironment for immune checkpoint blockade therapy.
Article in Journal for immunotherapy of cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
46 citing papers in PubMed, 2 syntheses or guidelines pooled it, 58 citations in OpenAlex.
- Immune checkpoint inhibitor therapy in advanced cancer: clinical association of irAEs type, inflammatory markers and efficacy.Frontiers in immunology · 2025Pooled it
- Efficacy and safety of PD-1/PD-L1 inhibitor combined with chemotherapy versus chemotherapy alone in the treatment of advanced gastric or gastroesophageal junction adenocarcinoma: a systematic review and meta-analysis.Frontiers in oncology · 2023Pooled it
- Pemetrexed Maintenance versus Observation in Patients with Advanced Urothelial Carcinoma Who Completed First-Line Platinum-Based Chemotherapy without Disease Progression (PREMIER, KCSG GU16-05).Cancer research and treatment · 2025Trial
- Cancer Chemoimmunotherapy: Time Will Tell.Cancer immunology research · 2026Article
- Breakthroughs in HBV-related HCC Therapy: The Unmatched Potential of Immune Checkpoint Inhibitors.Current treatment options in oncology · 2026Review
- Article
- Liposomal glytrexate formulation: improving antitumour efficacy and minimizing toxicity in breast cancer therapy.International journal of pharmaceutics: X · 2025Article
- Article
- Suppression of tumor growth by GMI, an edible fungal immunomodulatory protein, is associated with targeting GSK3β‑mediated proteasomal degradation of PD‑L1.International journal of molecular medicine · 2025Article
- The dual role of ACE2 in viral infections and neurodegeneration: mechanisms and therapeutic opportunities.Journal of neurovirology · 2025Review
- Hyperthermia-induced cytotoxicity and modulation of PD-L1 and MHC-I expression in human non-small cell lung cancer cell lines.Experimental physiology · 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
- Harnessing nucleotide metabolism and immunity in cancer: a tumour microenvironment perspective.The FEBS journal · 2025Review
- Opportunities for Precision Dosing of Cytotoxic Drugs in Non-Small Cell Lung Cancer: Bridging the Gap in Precision Medicine.Clinical pharmacokinetics · 2025Review
- 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
- The administration sequences of immune checkpoint inhibitors and chemotherapy cause discrete efficacy when treating non-small cell lung cancer: a retrospective study.Frontiers in immunology · 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
- Diffuse and Strong TTF-1 Expression Predicts Response to Pemetrexed-Based Immunochemotherapy in Advanced Lung Adenocarcinoma.Cancer management and research · 2025Article
- Targeted inhibition of integrin αVβ3 induces cytotoxicity and suppresses migration ability in ovarian cancer cells and tumor spheroids.International journal of medical sciences · 2025Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe immune checkpoint blockade (ICB) targeting programmed cell death-1 (PD-1) and its ligand (PD-L1) has been proved beneficial for numerous types of cancers, including non-small-cell lung cancer (NSCLC). However, a significant number of patients with NSCLC still fail to respond to ICB due to unfavorable tumor microenvironment. To improve the efficacy, the immune-chemotherapy combination with pemetrexed, cis/carboplatin and pembrolizumab (anti-PD-1) has been recently approved as first-line treatment in advanced NSCLCs. While chemotherapeutic agents exert beneficial effects, the underlying antitumor mechanism(s) remains unclear.
methodsPemetrexed, cisplatin and other chemotherapeutic agents were tested for the potential to induce PD-L1 expression in NSCLC cells by immunoblotting and flow cytometry. The ability to prime the tumor immune microenvironment was then determined by NSCLC/T cell coculture systems and syngeneic mouse models. Subpopulations of NSCLC cells responding differently to pemetrexed were selected and subjected to RNA-sequencing analysis. The key signaling pathways were identified and validated in vitro and in vivo.
resultsPemetrexed induced the transcriptional activation of
conclusionsOur findings reveal novel mechanisms showing that pemetrexed upregulates PD-L1 expression and primes a favorable microenvironment for ICB, which provides a mechanistic basis for the combinatory chemoimmunotherapy in NSCLC treatment.
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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.