Enhanced antitumor efficacy through microwave ablation combined with a dendritic cell-derived exosome vaccine in hepatocellular carcinoma

Abstract

Aim: To investigate the antitumor efficacy of microwave ablation combined with dendritic cell-derived exosomes (Dex) or dendritic cells (DC) in treating hepatocellular carcinoma using a tumor-bearing mouse model. Methods: We used a bilateral tumor-bearing mouse model treated with MWA, MWA þ DC (DC-combined group) or MWA þ Dex (Dex-combined group). Following tumor ablation on one side, the tumor volume on the contralateral side was monitored. The proportions of CD8 þ (cytotoxic) T cells and regulatory T (Treg) cells in the spleen were analyzed by flow cytometry, and the number of CD8 þ T cells and Treg cells in tumor sites was detected by immunohistochemistry. The concentration of interleukin-10 and interferon-c in plasma was identified using enzyme-linked immunosorbent assay. Results: The combination therapy significantly inhibited tumor growth compared with MWA monotherapy. In addition, the tumor immune microenvironment was significantly improved in HCC mice in the combination therapy groups compared to MWA group demonstrated by an increased number of CD8 þ T cells and a decreased number of Treg cells in tumor sites. A lower proportion of Treg cells were observed in the spleen in the combination therapy groups compared to MWA group. Moreover, the concentration of plasma IFN-c increased, and the concentration of plasma IL-10 decreased in the combination therapy groups compared to the MWA group. However, there was no statistical difference between the Dex-combined group and the DC-combined group in the comparisons mentioned above. Conclusions: Our results provide evidence that MWA combined with Dex can significantly inhibit tumor growth and improve the immune microenvironment compared to MWA alone. Furthermore, the immune-enhancing effect of Dex and DC was equivalent in our combination therapy strategy.

Hyperthermia and Tumor Immunity

“…Similarly, when rechallenged in the contralateral flank with the same cell line, the combination therapy group showed an earlier tendency to suppress tumor growth compared with MWA alone. The second study [ 71 ] was designed similarly but included a dendritic cell-derived exosome group. They found no significant differences between MWA plus dendritic cells or MWA plus dendritic cell-derived exosomes: both groups resulted in higher levels of CD8+ T cells and IFN-γ and lower levels of Treg cells and IL-10 compared with MWA alone.…”

Exosomes as potential diagnosis and treatment for liver cancer

“…Table 5 [ 70 , 71 ] shows the self-derived exosomes from dendritic cells as potential therapeutic factors. Data showed exosomes isolated from dendritic cells could inhibit tumor growth and improve the immune response.…”

Exosome-Based Vaccines: History, Current State, and Clinical Trials

“…Additionally, this group showed that purified DEXs successfully carried melanoma epitopes and induced potent anti-tumor immune responses, thereby slowing tumor progression. Recently, a DEX-based vaccine combined with microwave ablation was reported to inhibit tumor growth in hepatocellular carcinoma (HCC) mouse models compared to microwave ablation (a common therapy for HCC patients) alone, in this case, the tumor disappeared 10 days after microwave ablation in combination with DEX injection (92). Additionally, HCC features a high expression level of a-fetoprotein (AFP), which has been used as an HCC antigen for monitoring and diagnosis (93).…”