Radiofrequency Ablation Does Not Induce the Significant Increase of CD4 + CD25 + Foxp3 + Regulatory T Cells Compared wit

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ORIGINAL ARTICLE

Radiofrequency Ablation Does Not Induce the Significant Increase of CD4+CD25+Foxp3+ Regulatory T Cells Compared with Surgical Resection in Hepal-6 Tumor Model Heng-Jun Gao • Yao-Jun Zhang • Hui-Hong Liang Peng Li • Zhen-Wei Peng • Xiong-Hao Pang • Min-Shan Chen



Received: 18 August 2012 / Accepted: 25 March 2013 / Published online: 18 April 2013 Ó L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland 2013

Abstract Surgical resection (SR) and radiofrequency ablation (RFA) are all currently recognized as important and effective treatment in solid tumors. This study aimed to investigate change in level of CD4?CD25?Foxp3? regulatory T (Treg) cells in tumor-bearing mice after SR vs. RFA and the relationship of this level with tumor progression. Hepa1-6 tumor cells were inoculated subcutaneously into C57BL/6J mice. The population of Treg cells was measured by flow cytometry at selected post-SR or post-RFA times. Tumor growth was measured by rechallenge in the contralateral flank. The tumor volume was calculated and compared with that of a control group. The correlation between the population of Treg cells and tumor volume was analyzed. A significant increase in Treg cells was observed after SR compared with the preoperative level, while the level after RFA was relatively stable. A significant difference in tumor growth between the SR and RFA groups was observed in the initial postoperative phase but not in the later phase. A correlation was found between tumor volume and level of Treg cells. Our study revealed that RFA stabilizes the level of Treg during postoperative recovery, whereas SR activates the

H.-J. Gao and Y.-J. Zhang contributed equally to this study. H.-J. Gao  Y.-J. Zhang  H.-H. Liang  P. Li  Z.-W. Peng  X.-H. Pang  M.-S. Chen (&) Department of Hepatobiliary Surgery, Cancer Centre of Sun Yat-Sen University, 651 Dongfeng Road East, Guangzhou 510060, People’s Republic of China e-mail: [email protected] H.-J. Gao  Y.-J. Zhang  H.-H. Liang  P. Li  Z.-W. Peng  X.-H. Pang  M.-S. Chen State Key Laboratory of Oncology in Southern China, Guangzhou 510060, People’s Republic of China

immunosuppressive reaction by upregulating the level of such cells, promoting tumor growth. Keywords Radiofrequency ablation  Surgical resection  Tumor progression  CD4?CD25?Foxp3? regulatory T cells  Animal model

Introduction Radiofrequency ablation (RFA) has been an important treatment for tumors, especially as curative therapy for hepatocellular carcinoma with a tumor diameter of B2 cm (Chen et al. 2006; Livraghi et al. 2008). Furthermore, RFA has been used successfully in the management of other malignancies, including renal cancer, lung cancer, and breast cancer (Crocetti and Lencioni 2010; Kinoshita et al. 2011; Tracy et al. 2010). These clinical studies raise the question of how RFA successfully destroys a tumor. Does it induce coagulation necrosis while also prompting a specific internal biological response? Surgical resection (SR) is a traditional primary curat