Abstract
BackgroundLocoregional therapy combined with systemic therapy can further improve the prognoses for HCC. However, the efficacy of TACE combined with ICIs and TKIs for HCC and whether this triple therapy can activate systemic immune response are still unknown.PurposeTo identify the efficacy of TACE+ICIs+TKIs for unresectable hepatocellular carcinoma (uHCC) and its effect on systemic immunity.Materials and MethodsThis single-center retrospective study was approved by the Institutional Review Board. From August 1, 2019, to March 30, 2021, patients with uHCC who received the combination therapy of TACE+ICIs+TKIs were included. Peripheral blood samples were collected at baseline and once a month for 4 months after treatment. Lymphocyte subsets were measured by flow cytometry. Immunoglobulins were measured using the immune turbidimetric method. The dynamic change trend of circulating parameters was tested using simple linear regression.ResultsFifty-three patients with a mean age of 59 ± 10.6 years were included. TTP was 8.0 months (95% CI, 5.5–10.5) and PFS was 8.5 months (95% CI, 5.4–11.5). ORR was 52.8% and DCR was 81.1%. Twenty patients had completed analysis of biomarkers in peripheral blood. For cellular immune response, the level of circulating CD8+, CD3+ T cells and NK cells increased, the frequency of CD4+T cells and the CD4+/CD8+ ratio decreased, and among them, CD8+ T cells increased significantly. For humoral immune response, there was a significant decrease in B cells and a significant increase in Ig G, Ig κ, and Ig λ. Moreover, Ig G, Ig κ, and Ig λ were related to tumor response.ConclusionTACE+ICIs+TKIs showed considerable efficacy in patients with uHCC. This triple therapy activated not only cell immune but also humoral immune activation. Circulating Ig G, Ig λ, and Ig κ can serve as potential biomarkers.
Highlights
The prognosis of hepatocellular carcinoma (HCC) still needs to be improved
We found that Ig G, Ig k, and Ig l increased at the time of response, and decreased again to the level of baseline with tumor progression
The combination of transarterial chemoembolization (TACE)+immune checkpoint inhibitors (ICIs) +Tyrosine kinase inhibitors (TKIs) resulted in an objective response rate (ORR) of 52.8% and a disease control rate (DCR) of 81.1%, with a time to progression (TTP) of 8.0 months and a progression-free survival (PFS) of 8.5 months
Summary
The prognosis of hepatocellular carcinoma (HCC) still needs to be improved. Only approximately 30% of HCC patients are diagnosed early enough to benefit from surgical resection [1]. For patients with unresected HCC (uHCC), transarterial therapies are the most commonly used treatment and can be divided into TAE (bland embolization without chemotherapy drugs), TACE (lipiodol mixed with chemotherapy drugs), dTACE (drug-eluting bead), and TARE (radioactive particles containing yttrium-90), according to different embolization materials. The complete response (CR) rate of TACE is limited [6], and residual tumor often require repeated TACE. For patients with a high tumor burden, a combination of systemic therapy is frequently required [8]. The efficacy of TACE combined with ICIs and TKIs for HCC and whether this triple therapy can activate systemic immune response are still unknown. Purpose: To identify the efficacy of TACE+ICIs+TKIs for unresectable hepatocellular carcinoma (uHCC) and its effect on systemic immunity
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