Lei Wang

Two-pronged microenvironmental modulation of metal-oxidase cascade catalysis and metabolic intervention for synergistic tumor immunotherapy

In Situ Formed Nanocomposite Hydrogel Improve Local Delivery of Antiangiogenic Agents and Immune Checkpoint Inhibitor for Cervical Carcinoma Therapy

Abstract Immune checkpoint blockade targeting the programmed cell death protein‐1 (PD‐1)/ligand (PD‐L1) axis has emerged as a promising therapeutic strategy for cervical carcinoma. However, its clinical application remains limited by the immunosuppressive tumor microenvironment (TME) and poor targeting efficiency, particularly in solid tumors. To address these challenges, a nanocomposite hydrogel system (Apa/BPNPs@Gel) is developed by encapsulating PD‐L1 inhibitor BMS202 nanoparticles coated with polyvinyl alcohol (BPNPs) into a polyvinyl alcohol/alginate hybrid hydrogel. This in situ formed hydrogel exhibits favorable biocompatibility and reactive oxygen species‐dependent sequential drug release. Initially, the antiangiogenic agent apatinib (Apa) is released to alleviate tumor hypoxia through vascular normalization and enhance PD‐L1 suppression, priming the TME for subsequent anti‐PD(L)1 therapy. The hydrogel framework extends the residence time of BMS202 (a skeleton component), improving therapeutic efficacy. Notably, in preclinical cervical carcinoma models, Apa/BPNPs@Gel mediated combination therapy significantly inhibited tumor growth and prolonged survival by activating tumor‐suppressed CD8+ T cells. Hence, this locally administrable hydrogel offers a versatile platform to modulate the immunosuppressive TME and enhance immunotherapeutic outcomes.

Prognostic significance of index (LANR) composed of preoperative lymphocytes, albumin, and neutrophils in patients with stage IB-IIA cervical cancer

Background The purpose of this study was to investigate the role of preoperative lymphocytes, albumin, neutrophils, and LANR in the prognosis of patients with stage IB-IIA cervical cancer (CC). Methods We made a retrospective analysis of the clinical information and related materials of 202 patients with stage IB-IIA primary cervical cancer who had undergone a radical hysterectomy in the Department of Gynecology at the Affiliated Hospital of Jiangnan University between January 2017 and December 2018. The definition of LANR was as follows: LANR, lymphocyte × albumin / neutrophil. The receiver operating characteristic curve (ROC) was generated to determine the best cut-off values for these parameters, as well as the sensitivity and specificity of LANR in predicting recurrence and survival. The Kaplan–Meier method was employed to draw survival curves in our survival analysis. Univariate analysis, multifactorial analysis, and subgroup analysis were used to evaluate the prognostic significance of LANR in overall and progression-free survival. Results The median follow-up time of the study was 55 months. In overall survival, the area under the curve for LANR was 0.704 (95% CI: 0.590–0.818, p<0.05). And in progression-free survival, the area under the curve for LANR was 0.745 (95% CI: 0.662–0.828, p<0.05). Univariate and multivariate analyses showed that the value of LANR was associated with both overall survival and progression-free survival (p< 0.05). Kaplan-Meier analysis demonstrated that OS (p< 0.001) and PFS (p< 0.001) in patients with high LANR levels were significantly higher than those with low LANR levels. Conclusions Our findings suggested that LANR might serve as a clinically reliable and effective independent prognostic indicator in patients with stage IB-IIA cervical cancer.