1. Introduction
Hepatocellular carcinoma (HCC) is the most common malignancy worldwide. Currently, liver transplantation and surgical resection remain the primary choice for HCC, but the overall survival of HCC patients is still depressing mainly due to local recurrence, distant metastasis, treatment resistance, and the lack of early diagnosis [1-3]. Transarterial chemoembolization (TACE) is one of the first-line treatment choices for HCC patients with specific clinical characteristics, such as stage B according to Barcelona Clinic Liver Cancer (BCLC)[4]. The transcatheter delivery of both chemotherapeutic agents and embolizing agents contributes to a dual effect of cytotoxicity and ischemia in tumor tissues [4]. Currently, there are mang TACE modalities in clinical practice, such as conventional TACE (cTACE) , GSMs-TACE and DEB-TACE. [4].
As the representative of absorbable particles, gelatn sponge microparticles are characterized by chemical cross-linking and physical adsorption since they can be absorbed 7-15 days after arterial embolization. Since 2009, satisfactory efficacy and safety of GSMs-TACE in the treatment of HCC patients at stage B and C (BCLC classification) with a diameter of 150 μm-350 μm/350 μm-560 μm GSMs have been achieved in our team [5, 6]. During GSMs-TACE procedures, under the premise of good liver function, the standard of terminating embolization is that the tumor blood supply artery is completely embolized. Compared with cTACE, the application of TACE combined with different microparticles in the treatment of liver cancer can lead to more significant tumor necrosis, especially the huge liver tumors.
Since the identification of tumor antigens, various approaches manipulating the immune system have been developed for cancer therapies [7]. However, not all patients respond to immunotherapies, and one of the major obstacles is the formation of immunosuppressive tumor microenvironment which is filled with immunosuppressive cells such as myeloid‐derived suppressor cells and regulatory T cells [8]. Treg cells are a T-lymphocyte subset and help maintain immune homeostasis by controlling abnormal/excessive immune responses. Studies have found that Treg cells are also involved in development and progression of tumors via acting as s suppressor of effective antitumor immunity [7, 9]. High infiltration by Treg cells into TME was observed in various types of tumors including HCC and was found to be correlated with poor prognosis [8-10]. Therefore, strategies to reduce Treg cells and control the functions of Treg cells would be potentially effective anticancer therapies.
Many studies have confirmed the efficacy and safety of TACE procedures in treating HCC, and it was considered that the effects were mainly attributed to the blood supply blockade and the cytotoxic effects [11, 12]. Except for the tumor necrosis, it was also observed that the lesions of extrahepatic metastasis were reduced or even disappeared as described in our clinical practice. Considering the close relationship between tumor metastasis and the immunosuppressive TME, these findings prompted us wonder if the effect of TACE was also partly attributed to that the tumor necrosis induced by TACE promoted the release of tumor antigens and then had some positive regulatory effects on the anticancer immunity. However, there have been no related studies to testify this hypothesis. Thus, this study aimed to determine the changes in immune function indicated by the peripheral Treg cell proportion in HCC patients after GSMs-TACE. The results of this study provided a piece of preliminary evidence that GSMs-TACE may be used in combination with immune adjuvant therapies to increase the efficacy of HCC treatment.