ArticleClinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico2023
Dipeptidyl peptidase 4 inhibitor reduces tumor-associated macrophages and enhances anti-PD-L1-mediated tumor suppression in non-small cell lung cancer.
Article in Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 25 citations in OpenAlex.
- A bibliometric analysis of research trends and hotspots regarding macrophage polarization in lung cancer.Journal of thoracic disease · 2026Article
- The Role of Dipeptidyl Peptidase Inhibitors in Pulmonary Diseases.Biomedicines · 2026Review
- Sitagliptin Modulates Functional and Phenotypic Properties of Human Neutrophils Under Normal- and High-Glucose Conditions In Vitro.Molecules (Basel, Switzerland) · 2026Article
- Identification and validation of DPP4 in predicting the prognosis of clear cell RCC.Discover oncology · 2026Article
- Sitagliptin Potentiates the Anticancer Activity of Doxorubicin Through ROS-Driven Apoptosis and MMP/TIMP Regulation in HeLa Cells.Pharmaceutics · 2025Article
- Repurposing DPP-4 inhibitors as anticancer agents in KRAS-mutated pancreatic ductal adenocarcinoma.BMC pharmacology & toxicology · 2025Article
- Dipeptidyl Peptidase 4 Restoration Facilitates Antitumor Immunity in KRAS-LKB1-Mutant Lung Cancer.Cancer research communications · 2025Article
- Incretin-Based Therapies and Cancer: What's New?Medicina (Kaunas, Lithuania) · 2025Review
- DPP4, a potential tumor biomarker, and tumor therapeutic target: review.Molecular biology reports · 2025Review
- The role and clinical significance of tumor-associated macrophages in the epithelial-mesenchymal transition of lung cancer.Frontiers in oncology · 2025Review
- Anti-Diabetic Therapies and Cancer: From Bench to Bedside.Biomolecules · 2024Review
- Exploring the Frequency and Risk Factors of Hyperprogressive Disease in Patients with Advanced Melanoma Treated with Immune Checkpoint Inhibitors.Current oncology (Toronto, Ont.) · 2024Article
- New Insights into the Pleiotropic Actions of Dipeptidyl Peptidase-4 Inhibitors Beyond Glycaemic Control.TouchREVIEWS in endocrinology · 2024Review
- Comparative effectiveness of sodium-glucose cotransporter-2 inhibitors for new-onset gastric cancer and gastric diseases in patients with type 2 diabetes mellitus: a population-based cohort study.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2024Article
- CXCR6-positive circulating mucosal-associated invariant T cells can identify patients with non-small cell lung cancer responding to anti-PD-1 immunotherapy.Journal of experimental & clinical cancer research : CR · 2024Article
- Detailed Characterization of the Lung-Gut Microbiome Axis Reveals the Link between PD-L1 and the Microbiome in Non-Small-Cell Lung Cancer Patients.International journal of molecular sciences · 2024Article
- Macrophage colony-stimulating factor and its role in the tumor microenvironment: novel therapeutic avenues and mechanistic insights.Frontiers in oncology · 2024Review
- A Systems Biology Approach Unveils a Critical Role of DPP4 in Upper Gastrointestinal Cancer Patient Outcomes.Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer · 2024Article
- Targeting tumor-associated macrophage: an adjuvant strategy for lung cancer therapy.Frontiers in immunology · 2023Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
purposeThe efficacy of immune checkpoint inhibitors such as programmed cell death ligand 1 (PD-L1) antibodies in non-small cell lung cancer (NSCLC) is limited, and combined use with other therapies is recommended. Dipeptidyl peptidase 4 (DPP4) inhibitors, a class of small molecule inhibitors, are highly effective for treating type 2 diabetes. Emerging evidence implicates DPP4 inhibitors as immunomodulators that modify aspects of innate and adaptive immunity. We evaluated the combination of a DPP4 inhibitor (anagliptin) and PD-L1 blockade in an NSCLC mouse model.
methodsThe effect of the combination of anti-PD-L1 and anagliptin was evaluated in subcutaneous mouse models of NSCLC. Tumor-infiltrating immune cells were analyzed by flow cytometry. Bone marrow-derived monocytes of C57BL/6 mice were isolated in vitro to examine the underlying mechanism of anagliptin on the differentiation and polarization of macrophage.
resultsAnagliptin dramatically improved the efficacy of PD-L1 antibody monotherapy by inhibiting macrophage formation and M2 polarization in the tumor microenvironment. Mechanistically, anagliptin suppressed the production of reactive oxygen species in bone marrow monocytes by inhibiting NOX1 and NOX2 expression induced by macrophage colony-stimulating factor, reduced late ERK signaling pathway activation, and inhibited monocyte-macrophage differentiation. However, the inhibitory effect was reactivated by lipopolysaccharide and interferon-gamma interacting with corresponding receptors during M1 macrophage polarization, but not M2.
conclusionsAnagliptin can enhance PD-L1 blockade efficacy in NSCLC by inhibiting macrophage differentiation and M2 macrophage polarization, and combination therapy may be a promising strategy for treating PD-L1 blockade therapy-resistant patients with NSCLC.
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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 Socratic graph.