AUTHOR=Wu Hao , Li Su-shu , Zhou Meijun , Jiang An-Na , He Yanni , Wang Song , Yang Wei , Liu Hongmei 

TITLE=Palliative Radiofrequency Ablation Accelerates the Residual Tumor Progression Through Increasing Tumor-Infiltrating MDSCs and Reducing T-Cell-Mediated Anti-Tumor Immune Responses in Animal Model

JOURNAL=Frontiers in Oncology

VOLUME=Volume 10 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.01308

DOI=10.3389/fonc.2020.01308

ISSN=2234-943X

ABSTRACT=Previous studies showed that radiofrequency ablation (RFA) has the favorable treatment efficacy for hepatocellular carcinoma (HCC) or colorectal liver metastases (CRLM). However, palliative RFA resulting from larger HCC or multiple CRLM further accelerated the progression of potential residual tumor, yet its mechanism was still unknown. In this study, it was investigated to determine the influence of myeloid-derived suppressor cells (MDSCs) on T-cell immune responses and tumor recurrence after palliative RFA (pRFA). Then, CT26 tumor models were used. The percentage of MDSCs in peripheral blood were analyzed by flow cytometry after pRFA. And the level of Th1 and Th2 cytokines were measured by ELISA through different treatments (n=4/group). The tumor-infiltrating MDSCs, dendritic cells and intracellular cytokines level were analyzed by IHC staining after different treatments. The functional CD8+ T cells was confirmed by the co-localization immunofluorescence staining. And, the long-term outcomes was also evaluated. The results showed that tumor models treated with pRFA displayed significant increases in the percentage of MDSC of peripheral blood and tumor infiltration. The level of TGF-β and IL-6 after pRFA was higher than that before pRFA by ELISA and IHC staining. After depleting MDSCs by combining with Abs, the pRFA+Abs group achieved higher level of Th1 cytokines, and greatly enhanced the infiltration of functional CD8+ T cells when compared with pRFA alone. Meanwhile, the depletion of MDSCs through combination with Abs also resulted in tumor regression. In conclusion, palliative RFA accelerates the residual tumor progression through increasing tumor-infiltrating MDSCs and reducing T-cell-mediated anti-tumor immune responses, which could provide a potential approach for delaying the tumor recurrence caused by palliative RFA.