ArticleBritish journal of cancer2025
Peripheral blood neutrophils contribute to Claudin18.2-specific CAR-T cell treatment resistance in advanced gastric cancer.
Article in British journal of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03874897 (An Open Label, Single/Multiple Dose Exploratory Clinical Study to Evaluate the Safety, Efficacy, and Cytokinetics of Autologous Humanized Anti-claudin18.2 Chimeric Antigen Receptor T Cell in Advanced Solid Tumor Subjects), which is not on this map. Cited by 7 papers.
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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.
An Open Label, Single/Multiple Dose Exploratory Clinical Study to Evaluate the Safety, Efficacy, and Cytokinetics of Autologous Humanized Anti-claudin18.2 Chimeric Antigen Receptor T Cell in Advanced Solid Tumor Subjects
Who cites it
7 citing papers in PubMed.
- Immune-inflammatory-fibrinogen score as a novel prognostic biomarker in patients with gastric cancer undergoing radical gastrectomy: a multicenter study.World journal of surgical oncology · 2026Trial
- The evolution of cellular-based immunotherapy in the treatment of gastric cancer: an overview of clinical trials.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Claudin18.2 and the PD-1/PD-L1 axis in gastric cancer: mechanistic insights and implications for combination immunotherapy.Journal of translational medicine · 2026Review
- WDR82 suppresses breast cancer progression by inhibiting ERK-driven chemokine expression and neutrophil infiltration.International journal of biological sciences · 2026Article
- Resistance mechanisms and countermeasures in CLDN18.2-positive tumors: from molecular networks to clinical practice.Frontiers in oncology · 2026Review
- Physiological, patho-physiological, and potential therapeutic roles for neutrophils in cancer & beyond.Frontiers in immunology · 2026Review
- Optimizing CAR T cell therapy for solid tumours: a clinical perspective.Nature reviews. Clinical oncology · 2025Review
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Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundClaudin18.2 (CLDN18.2)-specific chimeric antigen receptor (CAR)-T cell treatment holds promise for advanced gastric cancer (GC) but has variable efficacy. This study investigates the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) in CAR-T cell treatment and elucidates the molecular mechanisms of treatment resistance.
methodsGC patients treated with CLDN18.2-specific CAR-T cell treatment were analyzed. Outcomes included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Survival analyses utilized Kaplan-Meier methods, log-rank tests, and Cox regression. Single-cell RNA sequencing was performed on peripheral blood samples to investigate the mechanisms of pro-tumor circulating neutrophils.
resultsElevated NLR was significantly associated with lower ORR (34.2% vs. 55.9%, P < 0.001), shorter median PFS (3.6 vs. 8.0 months, P < 0.001), and OS (5.6 vs. 13.8 months, P < 0.001). Single-cell sequencing identified a circulating neutrophil subcluster (NE-3) linked to disease progression. NE-3 expressed pro-tumoral factors (MMP-9), and was enriched in the IL-17 signaling pathway. The cellular interactions between neutrophils and T cells were more prominent in progression disease (PD) group than in partial response (PR) group.
conclusionsThis study highlights NLR as a significant prognostic factor in advanced GC patients receiving CLDN18.2-specific CAR-T cell treatment and provides insights into neutrophil-mediated treatment resistance. Further validation and exploration of strategies to mitigate neutrophil-induced immunosuppression are needed.
trial registrationNCT03874897.
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