Fig 3 -

(A) Mean value of the predictive temperature by month. (B) Predictive serum log 25(OH)D concentration according to monthly mean temperature. Black solid line indicates monthly mean value of predicted temperature; blue dotted line indicates 95% confidence interval for predictive value.</p

Plots of 25(OH)D according to age groups during the study period.

Plots of 25(OH)D according to age groups during the study period.</p

Baseline characteristics according to vitamin D status.

Baseline characteristics according to vitamin D status.</p

Monthly mean predicted log 25(OH)D value after adjusting for age, measured between January 2013 and December 2015.

Black solid line indicates monthly mean predicted log serum vitamin D (25(OH)D, ng/mL) value; blue dotted line indicates 95% confidence interval of predictive value.</p

Regression analyses of 25(OH)D with log transformation on the variables.

Regression analyses of 25(OH)D with log transformation on the variables.</p

Immunogenic Extracellular Vesicles Derived from Endoplasmic Reticulum-Stressed Tumor Cells: Implications as the Therapeutic Cancer Vaccine

Tumor-derived extracellular vesicles (TDEs) have potential for therapeutic cancer vaccine applications since they innately possess tumor-associated antigens, mediate antigen presentation, and can incorporate immune adjuvants for enhanced vaccine efficacy. However, the original TDEs also contain immune-suppressive proteins. To address this, we proposed a simple yet powerful preconditioning method to improve the overall immunogenicity of the TDEs. This approach involved inducing endoplasmic reticulum (ER) stress on parental tumor cells via N-glycosylation inhibition with tunicamycin. The generated immunogenic TDEs (iTDEs) contained down-regulated immunosuppressive proteins and up-regulated immune adjuvants, effectively activating dendritic cells (DCs) in vitro. Furthermore, in vivo evidence from a tumor-bearing mouse model showed that iTDEs activated DCs, enabling cytotoxic T lymphocytes (CTLs) to target tumors, and eventually established a systemic antitumor immune response. Additionally, iTDEs significantly delayed tumor recurrence in a postsurgery model compared with control groups. These findings highlight the immense potential of our strategy for utilizing TDEs to develop effective cancer vaccines