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.