Serum cytokines and creatinine/cystatin C ratio as prognostic biomarkers in advanced cancer patients treated with anti-PD-1/PD-L1 therapy.

OBJECTIVE: Immune checkpoint inhibitors (ICIs), specifically targeting the programmed cell death protein-1 or its ligand (PD-1/PD-L1), have been extensively used in the treatment of a spectrum of malignancies, although the predictive biomarkers remain to be elucidated. This study aims to investigate the association between baseline circulating levels of cytokines and the creatinine/cystatin C ratio (CCR) with the treatment outcomes of ICIs in patients with advanced cancer. METHODS: The pre-treatment circulating levels of 10 cytokines (PD-L1, CTLA4, CXCL10, LAG3, HGF, CCL2, MIG, GRANB, IL-18, and IL-6) were measured via automated capillary-based immunoassay platform in the serum of 65 advanced cancer patients treated with anti-PD-1/PD-L1-based systemic therapy and 10 healthy volunteers. The levels of cytokines and CCR were quantified and categorized into high and low groups based on the median value. The associations of serum cytokines and CCR with response to treatment, survival, and immune-related adverse events were assessed. RESULTS: Elevated circulating levels of 6 cytokines (PD-L1, CXCL10, HGF, CCL2, MIG, and IL-6) were observed in cancer patients compared with that in healthy volunteers. The correlation coefficients between cytokines, CCR and nutritional risk index were also calculated. In the cancer cohort (N = 65), low circulating HGF (P = 0.023, P = 0.029), low IL-6 (P = 0.002, P < 0.001), and high CCR (P = 0.031, P = 0.008) were associated with significantly improved progression-free survival (PFS) and overall survival (OS). Multi-variable COX analyses adjusted for clinicopathological factors revealed that low HGF, low IL-6, and high CCR were independent favorable prognostic factors for PFS (P = 0.028, P = 0.010, and P = 0.015, respectively) and OS (P = 0.043, P = 0.003, and P = 0.026, respectively). Grade 2 irAEs occurred more frequently in patients with low levels of circulating CCL2 and LAG3. CONCLUSIONS: Pre-treatment circulating levels of serum IL-6, HGF, and CCR may serve as independent predictive and prognostic biomarkers in advanced cancer patients treated with ICIs-based systemic therapy. These findings might help to identify potential patients who would benefit from these therapies.

Poly(2-hydroxyethyl methacrylate) wound dressing containing ciprofloxacin and its drug release studies.

An improved wound dressing with a long-term drug diffusion-efficacy has been developed by UV-radiation technique. It involves incorporation of ciprofloxacin (CIP), at the concentration of 0.5-2.0% (w/v), into a water mixture of 2-hydroxymethacrylate (HEMA) monomer, benzoin isobutyl ether (BIE) initiator and different content of ethylene glycol dimethacrylate (EGDMA) cross-linker. Increasing the concentration of EGDMA would reduce the releasing ratio of CIP from pHEMA. T1/2 is increased from 2.64 to 45.67 h when the EGDMA is added from 1 to 8%. In the ranges of 0< or = F < or = 0.6, the n value of 1%CIP-pHEMA membranes is increased from 0.48 to 0.81. It indicates that the mechanism of drug release falls between the Fickian and Case II diffusion model. The antibacterial activity of the drug impregnated into the membrane was evaluated by in vitro drug kinetic agar plate method. Higher concentration of EGDMA, up to 8% of the cross-linker, extends the drug release. Comparison with the drug-soaked membranes, the newly synthesized 1% CIP-pHEMA membrane (cross-linked with 4% EGDMA) sustains the release of the entrapped drug and maintains the antibacterial activity up to 12 days.