Haptoglobin promoter polymorphism rs5472 as a prognostic biomarker for peptide vaccine efficacy in castration-resistant prostate cancer patients.

Personalized peptide vaccination (PPV) is an attractive approach to cancer immunotherapy with strong immune-boosting effects conferring significant clinical benefit. However, as with most therapeutic agents, there is a difference in clinical efficacy among patients receiving PPV. Therefore, a useful biomarker is urgently needed for prognosticating clinical outcomes to preselect patients who would benefit the most from PPV. In this retrospective study, to detect a molecular prognosticator of clinical outcomes for PPV, we analyzed whole-genome gene expression profiles of peripheral blood mononuclear cells (PBMCs) in castration-resistant prostate cancer (CRPC) patients before administration of PPV. Cox regression analysis revealed that mRNA expression of myeloperoxidase, haptoglobin, and neutrophil elastase was significantly associated with overall survival (OS) among vaccinated CRPC patients (adjusted P < 0.01). By promoter sequence analysis of these three genes, we found that rs5472 of haptoglobin (HP), an acute-phase plasma glycoprotein, was strongly correlated to OS of vaccinated CRPC patients (P = 0.0047, hazard ratio 0.47; 95 % confidence interval 0.28-0.80). Furthermore, both HP mRNA expression in PBMCs and protein level in plasma of CRPC patients before administration of PPV exhibited rs5472 dependence (P < 0.001 for mRNA expression and P < 0.05 for protein level). Our findings suggest that rs5472 may play an important role in the immune response to PPV via regulation of HP. Thus, we concluded that rs5472 is a potential prognostic biomarker for PPV.

Haptoglobin proved a prognostic biomarker in peripheral blood of patients with personalized peptide vaccinations for advanced castration-resistant prostate cancer.

Haptoglobin (Hp) is a well-known acute-phase protein that possibly has influence on tumors through the immune response. This study was conducted to evaluate the correlation between Hp expression and the effect of treatment by cancer peptide vaccines in advanced castration-resistant prostate cancer (CRPC) patients. Hp expression was measured by RT-PCR using peripheral blood mononuclear cells (PBMCs) collected from advanced CRPC patients, who were divided into two groups: long-term survivors and short-term survivors. Before cancer peptide vaccination (pre-vaccination), Hp expression was almost same in the two groups, but after cancer peptide vaccination (post-vaccination), Hp expression was higher in short-term survivors, suggesting that Hp expression in the PBMCs increased in short-term survivors after treatment by cancer peptide vaccines. Our results suggest that Hp expression level in the PBMCs can serve as a prognostic biomarker in treatment by cancer peptide vaccine in advanced CRPC patients.

Ultralong lifetime and efficient room temperature phosphorescent carbon dots through multi-confinement structure design.

Room temperature phosphorescence materials have inspired extensive attention owing to their great potential in optical applications. However, it is hard to achieve a room temperature phosphorescence material with simultaneous long lifetime and high phosphorescence quantum efficiency. Herein, multi-confined carbon dots were designed and fabricated, enabling room temperature phosphorescence material with simultaneous ultralong lifetime, high phosphorescence quantum efficiency, and excellent stability. The multi-confinement by a highly rigid network, stable covalent bonding, and 3D spatial restriction efficiently rigidified the triplet excited states of carbon dots from non-radiative deactivation. The as-designed multi-confined carbon dots exhibit ultralong lifetime of 5.72 s, phosphorescence quantum efficiency of 26.36%, and exceptional stability against strong oxidants, acids and bases, as well as polar solvents. This work provides design principles and a universal strategy to construct metal-free room temperature phosphorescence materials with ultralong lifetime, high phosphorescence quantum efficiency, and high stability for promising applications, especially under harsh conditions.