Radiofrequency ablation (RFA) is the most common approach to thermal ablation for cancer therapy. Unfortunately, its efficacy is limited by incomplete ablation, and further optimization of RFA is required. Here, we demonstrate that incubation at 65°C triggers more EG7 tumor cell death by necrosis than treatment at 45°C, and the 65°C-treated cells are more effective at inducing antigenspecific CD8 + cytotoxic T lymphocyte (CTL) responses after injection in mice than the 45°C-treated ones. Dendritic cells (DCs) that phagocytose 65°C-treated EG7 cells become mature with upregulated MHCII and CD80 expression and are capable of efficiently inducing effector CTLs in mouse tumor models. RFA (65°C) therapy of EG7 tumors induces large areas of tumor necrosis and stimulates CTL responses. This leads to complete regression of small (~100 mm 3) tumors but fails to suppress the growth of larger (~350 mm 3) tumors. The administration of the Toll-like receptor-9 (TLR9) agonist unmethylated cytosine-phosphorothioate-guanine oligonucleotide (CpG) to DCs phagocytosing 65°C-treated EG7 cells enhances the expression of MHCII and CD40 on DCs as well as DC-induced stimulation of CTL responses. Importantly, the intratumoral administration of CpG following RFA also increases the frequencies of tumor-associated immunogenic CD11b − CD11c + CD103 + DC2 and CD11b + F4/80 + MHCII + M1 macrophages and increases CD4 + and CD8 + T-cell tumor infiltration, leading to enhanced CD4 + T cell-dependent CTL responses and potent inhibition of primary RFA-treated or distant untreated tumor growth as well as tumor lung metastasis in mice bearing larger tumors. Overall, our data indicate that CpG administration, which enhances RFA-induced CTL responses and ultimately potentiates the inhibition of primary tumor growth and lung metastasis, is a promising strategy for improving RFA treatment, which may assist in optimizing this important cancer therapy.
The hydrothermal system plays a crucial role in material and energy cycling between the lithosphere and hydrosphere. In general, seafloor hydrothermal systems are one of important Mg sinks, but the situation may not be the same as it is in terrestrial hydrothermal systems. In addition, the behavior of Mg isotopes during hydrothermal circulation is still unclear. Thus, in this study, we determined the Mg isotopic compositions of the hydrothermal fluids discharged in the Tengchong region to understand better the fate of Mg in the continental hydrothermal system. The δ2H and δ18O values of the Tengchong hydrothermal fluids indicate that the recharge water sources are primary from meteoric water and influenced by the evaporation process. In contrast, the subduction−related volcanic water input is limited, except in for the Rehai area. The Mg in most of the samples is contributed by percolated meteoric water. The measured δ26Mg values range from –0.969 to 0.173‰, which are enriched in light Mg compared to the volcanic rocks of Tengchong. Combined with the precipitation dissolution of carbonate, we calculated the δ26Mg value for the endmember fluid before precipitation, which shows that the process of carbonate precipitation changes the Mg isotope of the fluid, substantially. The Shiqiang (SQ) vent is unique among all of the samples, characterized by an extremely a high δ26Mg value and Mg concentration, and it is estimated that it could have been mixed with an upper crustal material. This also reveals the diversity of the hydrothermal fluid material sources in the subduction zone.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.