PDF(Pubmed)
Abstract：
BACKGROUND: The combination of transcatheter arterial chemoembolization (TACE) and tyrosine kinase inhibitors (TKIs) has shown broad prospects in prolonging the survival of patients with hepatocellular carcinoma (HCC). TACE and TKIs can affect the immune microenvironment in patients with HCC.
OBJECTIVE: To determine the overall effects and differences between TACE and different TKIs combinations on the immune microenvironment.
METHODS: Data and immune cell profile test results from 213 HCC patients treated with TACE combined with apatinib, lenvatinib, sorafenib, or donafenib before and after 3 wk of treatment were collected. Monocytes were co-cultured with LM3 liver cancer cells, and their ability to inhibit cancer cell growth was analyzed using the MTT method and a nude mouse subcutaneous tumorigenesis experiment. Simulated combined therapy was done using an in situ liver cancer C57BL/6 male mouse model, and the immune response of tumor tissues was analyzed using immunohistochemistry.
RESULTS: Compared to before combination therapy, the proportion of programmed cell death protein 1 (PD-1)+ mononuclear cells and the number of CD4+ T cells decreased in the TACE + apatinib group, while the number of absolute count of CD4+ and CD8+ T cells increased in the TACE + lenvatinib group. Furthermore, the number of regulatory cells decreased in the TACE + donafenib group, whereas the number of CD8+ T and natural killer cells increased. Additionally, monocytes in the TACE combined with donafenib or lenvatinib groups had a stronger ability to inhibit cancer cell growth than those in the other groups. Combining TACE with donafenib or lenvatinib increased CD8+ T cell infiltration into the tumor tissue. In addition, the proportion of PD-1+ in CD8+ cells, absolute CD8+ T lymphocyte count, and regulatory T cells proportion were independent prognostic factors affecting the survival time of patients with HCC.
CONCLUSIONS: TACE, in combination with different TKIs, produces different immune responses. Specifically, TACE combined with donafenib or lenvatinib may induce strong anti-tumor immune responses.
OBJECTIVE: To determine the overall effects and differences between TACE and different TKIs combinations on the immune microenvironment.
METHODS: Data and immune cell profile test results from 213 HCC patients treated with TACE combined with apatinib, lenvatinib, sorafenib, or donafenib before and after 3 wk of treatment were collected. Monocytes were co-cultured with LM3 liver cancer cells, and their ability to inhibit cancer cell growth was analyzed using the MTT method and a nude mouse subcutaneous tumorigenesis experiment. Simulated combined therapy was done using an in situ liver cancer C57BL/6 male mouse model, and the immune response of tumor tissues was analyzed using immunohistochemistry.
RESULTS: Compared to before combination therapy, the proportion of programmed cell death protein 1 (PD-1)+ mononuclear cells and the number of CD4+ T cells decreased in the TACE + apatinib group, while the number of absolute count of CD4+ and CD8+ T cells increased in the TACE + lenvatinib group. Furthermore, the number of regulatory cells decreased in the TACE + donafenib group, whereas the number of CD8+ T and natural killer cells increased. Additionally, monocytes in the TACE combined with donafenib or lenvatinib groups had a stronger ability to inhibit cancer cell growth than those in the other groups. Combining TACE with donafenib or lenvatinib increased CD8+ T cell infiltration into the tumor tissue. In addition, the proportion of PD-1+ in CD8+ cells, absolute CD8+ T lymphocyte count, and regulatory T cells proportion were independent prognostic factors affecting the survival time of patients with HCC.
CONCLUSIONS: TACE, in combination with different TKIs, produces different immune responses. Specifically, TACE combined with donafenib or lenvatinib may induce strong anti-tumor immune responses.
摘要：
背景：经导管动脉化疗栓塞（TACE）和酪氨酸激酶抑制剂（TKIs）的联合应用在延长肝细胞癌（HCC）患者的生存期方面显示出广阔的前景。TACE和TKIs可影响HCC患者的免疫微环境。
目的：确定TACE和不同TKI组合对免疫微环境的总体影响和差异。
方法：TACE联合阿帕替尼治疗的213例HCC患者的数据和免疫细胞谱测试结果，lenvatinib,索拉非尼,或多纳非尼治疗前和治疗后3周收集。单核细胞与LM3肝癌细胞共培养，用MTT法和裸鼠皮下肿瘤发生实验分析了它们抑制癌细胞生长的能力。使用原位肝癌C57BL/6雄性小鼠模型进行模拟联合治疗，用免疫组织化学方法分析肿瘤组织的免疫反应。
结果：与联合治疗前相比，TACE+阿帕替尼组程序性细胞死亡蛋白1(PD-1)+单核细胞比例和CD4+T细胞数量减少,而TACE+lenvatinib组CD4+和CD8+T细胞的绝对计数增加。此外，TACE+多纳非尼组调节性细胞数量减少，而CD8+T细胞和自然杀伤细胞的数量增加。此外,TACE联合多纳非尼或乐伐替尼组的单核细胞比其他组具有更强的抑制癌细胞生长的能力。联合TACE与多纳非尼或乐伐替尼增加了CD8+T细胞向肿瘤组织的浸润。此外,CD8+细胞中PD-1+的比例，CD8+T淋巴细胞绝对计数，调节性T细胞比例是影响HCC患者生存时间的独立预后因素。
结论：TACE，结合不同的TKIs，产生不同的免疫反应。具体来说,TACE联合多纳非尼或乐伐替尼可能诱导强烈的抗肿瘤免疫反应。
目的：确定TACE和不同TKI组合对免疫微环境的总体影响和差异。
方法：TACE联合阿帕替尼治疗的213例HCC患者的数据和免疫细胞谱测试结果，lenvatinib,索拉非尼,或多纳非尼治疗前和治疗后3周收集。单核细胞与LM3肝癌细胞共培养，用MTT法和裸鼠皮下肿瘤发生实验分析了它们抑制癌细胞生长的能力。使用原位肝癌C57BL/6雄性小鼠模型进行模拟联合治疗，用免疫组织化学方法分析肿瘤组织的免疫反应。
结果：与联合治疗前相比，TACE+阿帕替尼组程序性细胞死亡蛋白1(PD-1)+单核细胞比例和CD4+T细胞数量减少,而TACE+lenvatinib组CD4+和CD8+T细胞的绝对计数增加。此外，TACE+多纳非尼组调节性细胞数量减少，而CD8+T细胞和自然杀伤细胞的数量增加。此外,TACE联合多纳非尼或乐伐替尼组的单核细胞比其他组具有更强的抑制癌细胞生长的能力。联合TACE与多纳非尼或乐伐替尼增加了CD8+T细胞向肿瘤组织的浸润。此外,CD8+细胞中PD-1+的比例，CD8+T淋巴细胞绝对计数，调节性T细胞比例是影响HCC患者生存时间的独立预后因素。
结论：TACE，结合不同的TKIs，产生不同的免疫反应。具体来说,TACE联合多纳非尼或乐伐替尼可能诱导强烈的抗肿瘤免疫反应。
