Impact of Microparticle Transarterial Chemoembolization (mTACE) on myeloid-derived suppressor cell subtypes in hepatocellular carcinoma: Clinical correlations and therapeutic implications.

BACKGROUND: Myeloid-derived suppressor cells (MDSCs) play a pivotal role in immunosuppression and tumor progression in hepatocellular carcinoma (HCC). While various treatments like surgical resection, ablation, and radiotherapy have been studied for their effects on circulating MDSC frequencies in HCC patients, the findings remain inconclusive. Transarterial Chemoembolization (TACE) stands as the standard care for unresectable HCC, with Microparticle TACE (mTACE) gaining prominence for its capacity to induce significant tumor necrosis. However, the immunological ramifications of such pathological outcomes are scarcely reported. METHODS AND RESULTS: This study aims to elucidate the alterations in MDSC subtypes, specifically monocytic MDSCs (mMDSCs) and early-stage MDSCs (eMDSCs), post-mTACE and to investigate their clinical correlations in HCC patients. A cohort comprising 75 HCC patients, 16 liver cirrhosis patients, and 20 healthy controls (HC) was studied. Peripheral blood samples were collected and analyzed for MDSC subtypes. The study also explored the associations between MDSC frequencies and various clinical parameters in HCC patients. The frequency of mMDSCs was significantly elevated in the HCC group compared to liver cirrhosis and HC. Importantly, mMDSC levels were strongly correlated with aggressive clinical features of HCC, including tumor size, vascular invasion, and distant metastasis. Post-mTACE, a marked reduction in mMDSC frequencies was observed, while eMDSC levels remained stable. CONCLUSIONS: Our findings underscore the critical role of mMDSCs in HCC pathogenesis and their potential as a therapeutic target. The study also highlights the efficacy of mTACE in modulating the immunosuppressive tumor microenvironment, thereby opening new avenues for combinatorial immunotherapeutic strategies in HCC management.

Changes in the Peripheral Blood Treg Cell Proportion in Hepatocellular Carcinoma Patients After Transarterial Chemoembolization With Microparticles.

Objective: Transarterial chemoembolization (TACE) stands for an ideal therapy for patients with intermediate stage HCC. This study was carried out to observe the effect of microparticles-transarterial chemoembolization (microparticles-TACE, m-TACE) on the immune function of hepatocellular carcinoma (HCC) patients by detecting the proportion of regulatory (Treg) cells in the peripheral blood of HCC patients before and after m-TACE, and to determine whether m-TACE has a positive regulatory effect on the immune function of HCC patients. Methods: 33 HCC patients treated with Gelatn Sponge Microparticles (GSMs-TACE) were enrolled. Flow cytometry was used to determine the proportion of Treg cells and CD4+/CD8+ T cells in peripheral blood of HCC patients 1 day before GSMs-TACE, 1 to 2 weeks and 3 to 5 weeks after GSMs-TACE, respectively. Results: The Tregs cell proportion of HCC patients was significantly higher than that of the healthy and cirrhosis controls and was associated with various clinical indicators of HCC patients. The Treg cell proportion in HCC patients with BCLC stage C was higher than that of stage B patients; The Treg cell proportion at 1 to 2 weeks postoperatively was 8.54 ± 1.27%, which was significantly lower than that before the GSMs-TACE. The Treg cell proportion at 3 to 5 weeks postoperatively was 7.59 ± 1.27%, which continued to decline. The ratio of CD4+/CD8+ T cells was 1.31 ± 0.56, 1.86 ± 0.73, 1.76 ± 0.58% (P<0.01) respectively. Conclusion: These results indicated that m-TACE could exert a positive regulatory effect on the anticancer immune function of HCC patients, which may be used in combination with immune adjuvant therapies to enhance the efficacy of HCC.

Changes in the frequency of myeloid-derived suppressor cells after transarterial chemoembolization with gelatin sponge microparticles for hepatocellular carcinoma.

PURPOSE: A series of clinical studies have established the safety and efficacy of transcatheter arterial chemoembolization (TACE) with gelatin sponge microparticles (GSMs) in treating hepatocellular carcinoma (HCC). HCC can lead to obvious necrosis inside tumors, especially larger ones, although it is unclear whether such necrotic tumor tissue can induce favorable immune reactions against the tumor. Myeloid-derived suppressor cells (MDSCs) have immunosuppressive functions and are currently considered a very important cell type affecting tumor immunity. This study observed changes in MDSC frequency in peripheral blood before and after GSM-TACE to evaluate the effect on the immune function of HCC patients. METHODS: Eight patients diagnosed with HCC underwent GSM-TACE treatment in the Hepatobiliary Interventional Department of Beijing Tsinghua Chang Gung Hospital, Beijing, China; we followed up with the patients over a period of 30 days post-surgery. We used flow cytometry (FCM) to quantify the frequency of MDSCs in peripheral blood before TACE, 10 days after surgery and 30 days after surgery. RESULTS: MDSC frequency after GSM-TACE had a significant downward trend. Pre-TACE, it was 30.73% ±â€¯11.93%, decreasing to 18.60% ±â€¯11.37% at 10 days after operation. This decrease was not statistically significant (P > 0.05). MDSC frequency was even lower 30 days after TACE (7.63% ±â€¯7.32%) than at 10 days after TACE (P < 0.05), and there was a significant difference compared with pre-TACE (P < 0.001). We evaluated tumor response at 30 days after GSM-TACE according to the Modified Response Evaluation Criteria in Solid Tumors (mRECIST), and all eight patients showed partial response (PR). CONCLUSION: Our results confirmed that GSM-TACE was beneficial for improving anti-tumor immunity in the treatment of HCC.

Corrigendum to "Changes in the frequency of myeloid-derived suppressor cells after transarterial chemoembolization with gelatin sponge microparticles for hepatocellular carcinoma" [J. Interv. Med. 2 (2019) 21-26].

[This corrects the article DOI: 10.1016/j.jimed.2019.05.006.].