ArticlePakistan journal of medical sciences2026
Proliferative double-negative T (DNT)-cell responses to PD-1 blockade therapy were positively correlated with good clinical outcomes in non-small cell lung cancer patients.
Article in Pakistan journal of medical sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Objective: To explore the correlation between the frequency of circulating double-negative T cells (DNT) and clinical outcomes of tumor immunotherapy in non-small cell lung cancer (NSCLC) patients. Methodology: We conducted a retrospective, single-center study at Qingdao Central Hospital, China (from October 2020 to February 2023) involving a cohort of patients with advanced-stage NSCLC who received PD-1-targeted therapies. A basal and longitudinal analysis of peripheral DNT cells was performed on this cohort. The frequency and effector phenotypes of circulating DNT cells were examined using flow cytometry . The cytotoxicity of DNTs was assessed using DELFIA EuTDA cell cytotoxicity assay kits. Results: Flow cytometry analyses showed a marked reduction in circulating DNTs in patients with late-stage (III/IV) NSCLC compared to those with early-stage (I/II) disease. Interestingly, we observed an increase in Ki-67+ DNT cells in approximately 57% (29/51) of late-stage NSCLC patients following the first cycle of anti-PD-1 treatment, and these proliferating DNT cells exhibited effector-like phenotypes and enhanced cytotoxicity towards the lung adenocarcinoma cell line A549. Notably, 70.27% (26/37) of patients who experienced clinical benefits showed a responsive DNT cell profile within four weeks of starting therapy, but not 82.35% (14/17) of patients who developed disease progression. Strikingly, patients with early proliferative DNT cell responses had a longer overall survival (OS) than non-responders. The frequency of DNTs was positively correlated with a good clinical prognosis in patients receiving anti-PD-1 therapy. Conclusion: Analysis of pre- and post-treatment DNT cells revealed that a higher DNT cell count was associated with better prognosis. Our findings suggest that peripheral DNT cells may serve as valuable biomarkers for monitoring clinical responses in NSCLC patients undergoing anti-PD-1 therapy.
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