不完全微波消融（iMWA）后早期肿瘤复发的机制尚不清楚。据报道，抗程序性细胞死亡蛋白 1（抗 PD-1）单一疗法无法有效预防 iMWA 引起的残留肿瘤的进展。转化生长因子-β（TGFβ）信号通路在肿瘤的发生、发展中发挥着重要作用。我们假设在不完全 iMWA 后阻断转化生长因子-β 受体 (TGFβR) 可能会协同增强抗 PD-1 抗体的作用，以防止残留肿瘤的进展。我们用携带 Hepa1-6 衍生异种移植物的小鼠构建了 iMWA 模型。 iMWA后残留肿瘤中Tgfb1表达和磷酸化Smad3蛋白表达上调。随着TGFβR抑制剂SB431542的应用，细胞增殖潜力、肿瘤生长、上皮间质转化（EMT）标志物（包括Cdh2和Vim）和癌症干细胞标志物Epcam的mRNA表达以及浸润性Treg细胞均减少。残留肿瘤组织。此外，iMWA联合TGFβR阻断剂和抗PD-1抗体进一步降低了细胞增殖、肿瘤生长、EMT标志物和癌症干细胞标志物的表达以及残留肿瘤组织中的浸润Treg细胞。阻断TGFβR可以减轻肿瘤微环境的促肿瘤作用，从而显着阻止残留肿瘤组织的进展。我们的研究表明，阻断 TGFβR 可能是一种新的治疗策略，可增强抗 PD-1 抗体的效果，以预防 iMWA 后残留肝细胞癌 (HCC) 的进展。版权所有 © 2024 作者。由 Elsevier B.V. 出版。保留所有权利。

The mechanism of early tumor recurrence after incomplete microwave ablation (iMWA) is poorly understood. The anti-programmed cell death protein 1 (anti-PD-1) monotherapy is reported to be ineffective to prevent the progression of residual tumor resulted from iMWA. Transforming growth factor-β (TGFβ) signaling pathway plays an important role in tumorigenesis and development. We assume blocking transforming growth factor-β receptor (TGFβR) after incomplete iMWA may synergistically enhance the effect of anti-PD-1 antibody to prevent the progression of residual tumor. We construct an iMWA model with mice harboring Hepa1-6 derived xenograft. The Tgfb1 expression and phosphorylated-Smad3 protein expression is upregulated in the residual tumor after iMWA. With the application of TGFβR inhibitor SB431542, the cell proliferation potential, the tumor growth, the mRNA expression of epithelial mesenchymal transition (EMT) markers including Cdh2, and Vim, and cancer stem cell marker Epcam, and the infiltrating Treg cells are reduced in the residual tumor tissue. In addition, iMWA combined with TGFβR blocker and anti-PD-1 antibody further decreases the cell proliferation, tumor growth, expression of EMT markers and cancer stem cell marker, and the infiltrating Treg cells in the residual tumor tissue. Blocking TGFβR may alleviate the pro-tumoral effect of tumor microenvironment thereby significantly prevents the progression of residual tumor tissue. Our study indicates that blocking TGFβR may be a novel therapeutic strategy to enhance the effect of anti-PD-1 antibody to prevent residual hepatocellular carcinoma (HCC) progression after iMWA.Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.