Department of Interventional and Pain, Beijing Luhe Hospital, Capital Medical University, Beijing, China.
Hepatobiliary Interventional Department, Beijing Tsinghua Chang Gung Hospital Affiliated to Tsinghua University, Beijing, China.
Immun Inflamm Dis. 2024 Sep;12(9):e70007. doi: 10.1002/iid3.70007.
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.
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.
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.
髓系来源抑制细胞（MDSCs）在肝癌（HCC）的免疫抑制和肿瘤进展中起着关键作用。虽然已经研究了各种治疗方法，如手术切除、消融和放疗，以了解它们对 HCC 患者循环 MDSC 频率的影响，但结果仍不确定。经动脉化疗栓塞（TACE）是不可切除 HCC 的标准治疗方法，微球 TACE（mTACE）因其诱导显著肿瘤坏死的能力而受到关注。然而，这种病理结果的免疫学后果几乎没有报道。
本研究旨在阐明 mTACE 后 HCC 患者 MDSC 亚型（单核细胞来源 MDSC[mMDSC]和早期 MDSC[eMDSC]）的变化，并研究其与临床的相关性。研究纳入了 75 例 HCC 患者、16 例肝硬化患者和 20 例健康对照者（HC）。采集外周血样本来分析 MDSC 亚型。研究还探讨了 HCC 患者 MDSC 频率与各种临床参数之间的相关性。与肝硬化和 HC 相比，HCC 组的 mMDSC 频率明显升高。重要的是，mMDSC 水平与 HCC 的侵袭性临床特征，包括肿瘤大小、血管侵犯和远处转移密切相关。mTACE 后，mMDSC 频率明显降低，而 eMDSC 水平保持稳定。
我们的研究结果强调了 mMDSC 在 HCC 发病机制中的关键作用及其作为治疗靶点的潜力。研究还强调了 mTACE 调节免疫抑制性肿瘤微环境的疗效，为 HCC 管理的联合免疫治疗策略开辟了新途径。
