ORIGINAL RESEARCH article
Front. Med.
Sec. Obstetrics and Gynecology
Volume 12 - 2025 | doi: 10.3389/fmed.2025.1693436
Prospective Cohort Study on Predictors and Reversal Strategies for PD-1 Inhibitor Resistance in Advanced Cervical Cancer
Provisionally accepted
- First Affiliated Hospital of Hebei North University, Zhangjiakou, China
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Background: Resistance to PD-1 inhibitors remains a major barrier to effective immunotherapy in advanced cervical cancer. Early identification of predictive factors and exploration of reversal strategies are essential to optimize treatment outcomes. Methods: This prospective cohort study enrolled 140 patients with histologically confirmed advanced cervical cancer who received ≥2 cycles of PD-1 inhibitor–based therapy. Baseline clinical and laboratory data—including neutrophil-to-lymphocyte ratio (NLR), lactate dehydrogenase (LDH), and treatment history—were analyzed. Logistic and Cox regression models were used to identify predictors of resistance and survival outcomes. Predictive performance was assessed by ROC analysis with bootstrap validation. Results: A total of 140 patients with advanced cervical cancer were analyzed (median follow-up 24.3 months); 72 (51.4%) were PD-1–sensitive and 68 (48.6%) were resistant. Resistant patients showed higher baseline NLR (4.10 vs. 2.95, P<0.001) and more prior chemotherapy (67.6% vs. 45.8%, P=0.011). Multivariate analysis identified elevated NLR (OR 1.72, 95% CI 1.34–2.20), increased LDH (OR 1.28, 95% CI 1.01–1.64), and prior chemotherapy (OR 2.31, 95% CI 1.11–4.80) as independent predictors of resistance. The combined model (NLR + LDH + PD-L1 + chemotherapy) showed excellent discrimination (AUC 0.948; bootstrap 0.942). PD-1–sensitive patients had significantly longer PFS (14.8 vs. 5.6 months) and OS (32.4 vs. 15.7 months; both P<0.001). Among 18 resistant patients receiving PD-1–based combination therapy, the disease control rate was 72.2% and median PFS 5.8 months. Findings remained consistent across sensitivity and subgroup analyses. Conclusions: Elevated baseline NLR and LDH levels and prior chemotherapy exposure are strong predictors of PD-1 inhibitor resistance in cervical cancer. Incorporating these inflammatory biomarkers into risk-stratified management may improve patient selection and guide early combination interventions to overcome resistance.
Keywords: PD-1 inhibitor, cervical cancer, systemic inflammation, predictive model, LDH, NLR, Immunotherapy resistance
Received: 27 Aug 2025; Accepted: 22 Oct 2025.
Copyright: © 2025 Xiaoyan, Xiaojuan, Shijiao and Xiaofan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Zhao Xiaoyan, zhaoxiaolansjnk@163.com
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