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.

Seasonal variation and source identification of heavy metal(loid) contamination in peri-urban farms of Hue city, Vietnam.

This study focused on the seasonal variation and source identification of heavy metals (HMs) while considering effects of municipal wastewater (MWW) in peri-urban farms of Hue city, central Vietnam. Moreover, associated non-carcinogenic and carcinogenic health risks from consuming vegetables containing HMs were also assessed considering the hazard quotient and cancer risk, respectively. Therefore, concentrations of Fe, Mn, Zn, Cu, Cr, Cd, Pb, and As were determined in irrigation water, soil, and lettuce samples collected during dry and wet seasons from one upstream site where irrigation water has no impact on MWW as well as from two downstream sites in farms on the outskirt of the city. Although irrigation water and soil in the same farms were not polluted as strongly, lettuce samples were polluted with Cd, Zn, and Pb. Furthermore, levels of soil Cu and As and HMs (except for Cu) in lettuce in the wet season were significantly higher (p < 0.05) than those in the dry season, indicating the impact of MWW with seasonal change. The health risk assessment via lettuce consumption demonstrated an unacceptable carcinogenic risk owing to Cd and a cumulative non-carcinogenic risk owing to selected HMs in the lettuce, while all other risks were negligible. Correlation and principal component analyses were performed to identify HM sources, indicating that Cu, Zn, Cd, Pb, Cr, and As in irrigation water and soil could have anthropogenic sources (e.g., untreated MWW, fertilizer use); meanwhile, irrigation-water and soil Fe, Mn, As, and Cr could originate from non-anthropogenic sources (e.g., parent materials weathering). This study revealed that rapid urbanization together with high precipitation leading to urban floods in Hue city was a significant factor spreading HMs in agricultural farms, suggesting the importance of wastewater treatment system, which can reduce the HM load in the city to protect the local food production.