ArticleMedical oncology (Northwood, London, England)2019
Programmed death-1 receptor (PD-1) and PD-ligand-1 (PD-L1) expression in non-small cell lung cancer and the immune-suppressive effect of anaerobic glycolysis.
Article in Medical oncology (Northwood, London, England), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- Tumour-infiltrating lymphocytes: from prognosis to treatment selection.British journal of cancer · 2023Pooled it
- Article
- [Advances in Lactate Metabolic Reprogramming in Non-small Cell Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2026Review
- Glycolytic reprogramming in cancer: immune crosstalk, nutrient competition, and supportive care perspectives.Frontiers in immunology · 2026Review
- Immune-tumor cell ligand-receptor axes driving metabolic reprogramming and therapeutic resistance in cancer.Frontiers in immunology · 2026Review
- Development and validation of an immune-related gene set (IRGS) model for prognostic and immunotherapeutic assessment in lung adenocarcinoma (LUAD).Journal of thoracic disease · 2025Article
- Identification of prognostic-related tumor microenvironment genes in lung adenocarcinoma and establishment of a prognostic prediction model.Translational lung cancer research · 2025Article
- Potentiation of immune checkpoint blockade with a pH-sensitizer as monitored in two pre-clinical tumor models with acidoCEST MRI.British journal of cancer · 2025Article
- Construction and validation of immune prognosis model for lung adenocarcinoma based on machine learning.Frontiers in oncology · 2025Article
- Tumor-infiltrating lymphocytes in melanoma: from prognostic assessment to therapeutic applications.Frontiers in immunology · 2024Review
- Machine Learning in Diagnosis and Prognosis of Lung Cancer by PET-CT.Cancer management and research · 2024Review
- Acidosis-mediated increase in IFN-γ-induced PD-L1 expression on cancer cells as an immune escape mechanism in solid tumors.Molecular cancer · 2023Article
- Identification and validation of a PD-L1-related signature from mass spectrometry in gastric cancer.Journal of cancer research and clinical oncology · 2023Article
- Article
- PLEKHG2 Promotes NSCLC Cell Growth by Increasing Glycolysis via Activated PI3K/AKT Pathway.Journal of Cancer · 2023Article
- Mechanism of Bazhen decoction in the treatment of colorectal cancer based on network pharmacology, molecular docking, and experimental validation.Frontiers in immunology · 2023Article
- Decoding Roles of Exosomal lncRNAs in Tumor-Immune Regulation and Therapeutic Potential.Cancers · 2022Review
- Prognostic and Predictive Relevance of Tumor-Infiltrating Lymphocytes in Squamous Cell Head-Neck Cancer Patients Treated with Radical Radiotherapy/Chemo-Radiotherapy.Current oncology (Toronto, Ont.) · 2022Article
- Hypoxia-inducible factors: master regulators of hypoxic tumor immune escape.Journal of hematology & oncology · 2022Review
- Expression of CD47 and SIRPα Macrophage Immune-Checkpoint Pathway in Non-Small-Cell Lung Cancer.Cancers · 2022Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
The microenvironment of a tumor may regulate the anti-tumor immune response. Intratumoral acidosis and hypoxia may suppress lymphocyte proliferation and migration, and this may have important implications in modern immunotherapy. The expression of PD-L1 by cancer cells and of PD-1 by tumor infiltrating lymphocytes (TILs) was assessed in tissue specimens from 98 operable NSCLC patients. Their prognostic role and their association with makers of glycolysis and anaerobic metabolism were assessed. Strong cytoplasmic/membrane PD-L1 expression was noted in 45/98 cases. Intense presence of TILs was noted in 42/98 cases (high TIL-score), and intense presence of PD-1 expressing TILs (high PIL-score) in 17/98 cases. PD-L1 expression was directly correlated with high PIL-score (p = 0.005). A significant inverse relationship was found between lactate dehydrogenase LDH5 expression and PIL-score (p = 0.008). Similarly, low PIL-score was significantly linked with high-hexokinase HXKII and monocarboxylate transporter MCT2 expression (p < 0.04). Cases with both intense TIL-score and PIL-score had significantly better survival (p < 0.05). For patients with high TIL-score or high PIL-score, PD-L1 overexpression defined significantly poorer survival (p = 0.01 and p = 0.03, respectively). In multivariate analysis, stage (p = 0.002, HR 3.33, 95%CI 1.4-4.5) and TIL-score (p = 0.02, HR 2.12, 95%CI 1.1-4.0) were independent predictive variables of death events. Given the low specificity of PD-L1 as a biomarker for anti-PD-1/PD-L1 immunotherapy, a combined assessment of TIL, PD-L1, PD-1, and LDH5 provides a tool for an immunological/metabolic classification of NSCLC tumors, with a different prognosis and different expected response to anti-PD-1/PD-L1 immunotherapy, which should be considered in relevant clinical trials.
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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.