Purpose:
The aim of this study was to identify the prognostic value of blood neutrophil–lymphocyte ratio (NLR) in patients with advanced non-small-cell lung cancer (NSCLC) who received immune checkpoint blockade (ICB) therapy.
Materials and methods:
147 advanced NSCLC patients were enrolled in this study from June 30, 2013, to August 30, 2017. Survival analysis used the Kaplan and Meier methodology. The mean follow-up time was 2.6 years. The phenotypic T cells subtypes were evaluated by flow cytometry.
Results:
Of these patients, receiver operating characteristic (ROC) curves analysis were used to confirm the cut-off value, and patients were stratified into NLR>2.5 (n=88) and NLR≤2.5 (n=59) groups. Survival analysis showed that patients with NLR≤2.5 had significantly favorable overall survival (OS) and progression-free survival (PFS) compared with patients with NLR>2.5. After stratified with the tumor mutational burden (TMB), we further found that patients with NLR≤2.5 had significantly favorable OS and PFS compared with patients with NLR>2.5 in the group of patients with TMB>10, while in group patients with TMB≤10, patients with NLR≤2.5 had no significantly favorable OS and PFS compared with patients with NLR>2.5. The CD3
+
and CD8
+
/CD28
+
T cell subsets were significantly increased in patients with NLR≤2.5 (
P
<0.05), while the CD8
+
/CD28
−
and CD4
+
/CD25
+
cell subsets were significantly decreased in patients with NLR≤2.5 (
P
<0.05).
Conclusion:
High NLR value independently predicted poorer survival in advanced NSCLC patients received ICB therapy. The NLR may help oncologists to predict outcomes of patients received ICB and choose alternative therapies for patients with high NLR value.
Summary
Aims
The study reports the feasibility and efficiency of vascular endothelial growth factor (VEGF) delivery using nanoparticles synthesized from glycidyl methacrylated dextran (Dex‐GMA) and gelatin for therapeutic angiogenesis.
Methods
The nanoparticles were prepared using phase separation method, and the drug release profile was determined by ELISA study. The bioactivity of VEGF‐incorporated nanoparticles (VEGF‐NPs) were determined using tube formation assay. A rabbit hind limb ischemia model was employed to evaluate the in vivo therapeutic effect. Blood perfusion was measured by single‐photon emission computed tomography (SPECT). Vessel formation was evaluated by contrast angiography and immunohistochemistry.
Results
The nanoparticles synthesized were spherical in shape with evenly distributed size of about 130 ± 3.5 nm. The VEGF encapsulated was released in a biphase manner, with the majority of 69% released over 1–12 days. Tube formation assays showed increased tubular structures by VEGF‐NP compared with empty nanoparticles and no treatment. Both free VEGF and VEGF‐NP significantly increased blood perfusion compared with empty nanoparticles (both P < 0.001), but it was much higher in VEGF‐NP‐treated limbs (P < 0.001). Contrast angiography and immunohistological analysis also revealed more significant collateral artery formation and higher capillary density in VEGF‐NP‐treated limbs.
Conclusions
Dex‐GMA and gelatin‐based nanoparticles could provide sustained release of VEGF and may serve as a new way for angiogenesis.
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