Host antitumor resistance improved by the macrophage polarization in a chimera model of patients with HCC
Host antitumor resistance improved by the macrophage polarization in a chimera model of patients with HCC
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DOI：
10.1080/2162402x.2017.1299301
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发表时间：
2017-01-01
期刊：
影响因子：
7.2
通讯作者：
Suzuki, Fujio
中科院分区：
文献类型：
--
作者：
Asai, Akira;Tsuchimoto, Yusuke;Suzuki, Fujio
尽管在治疗和姑息治疗方面取得了重大进展，但肝细胞癌（HCC）仍然是全球癌症相关死亡的第三大原因。M1巨噬细胞（mphi）在HCC的宿主抗肿瘤防御中起关键作用。在我们的研究中，从四组HCC患者（组1,0期HCC患者；组2，A期HCC患者；组3，B期HCC患者；组4，C期HCC患者）的外周血中分离CD14（+）细胞并进行表型表征。然后，将2组和3组HCC患者的CD14（+）细胞诱导极化，并在HCC患者嵌合体模型中检测其抗肿瘤能力。人类HCC （HepG2实体瘤）在组3患者的嵌合体模型（组3 HCC嵌合体）中生长，但在组2患者的嵌合体模型（组2 HCC嵌合体）中没有生长。在HCC抗原的反应中，来自2组患者的大多数CD14（+）细胞（2组CD14（+）细胞）转换为M1表型(IL-12(+)IL-10（-)iNOS（+）细胞），而来自3组患者的大多数CD14（+）细胞（3组CD14（+）细胞）没有转换为M1表型，继续表达M2b表型特性(IL-12(-)IL-10(+)CCL1（+)iNOS（-）细胞）。CCL1反义寡脱氧核苷酸（ODN）处理后，组3 CD14（+）细胞呈现M1M phi极化。因此，我们的研究表明，CCL1反义ODN治疗后，3组HCC嵌合体的抗HCC防御能力有所提高。
Despite major advances in curative and palliative approaches, hepatocellular carcinoma (HCC) is still the third leading cause of cancer-related death worldwide. M1 macrophages (M phi) play a key role in host antitumor defenses in HCC. In our study, CD14(+) cells were isolated from the peripheral blood of four groups of HCC patients (group-1, patients with stage 0 HCC; group-2, patients with stage A HCC; group-3, patients with stage B HCC; and group-4, patients with stage C HCC) and characterized phenotypically. Then, CD14(+) cells from group-2 and group-3 HCC patients were induced to polarize and tested for their antitumor abilities in a chimera model of HCC patients. Human HCCs (HepG2 solid tumors) grew in a chimera model of group-3 patients (group-3 HCC chimeras) but not in a chimera model of group-2 patients (group-2 HCC chimeras). In response to HCC antigens, the majority of CD14(+) cells from group-2 patients (group-2 CD14(+) cells) switched to the M1 phenotype (IL-12(+)IL-10(-)iNOS(+)cells), whereas the majority of CD14(+) cells from group-3 patients (group-3 CD14(+) cells) did not switch to the M1 phenotype and continued to express M2b phenotypic properties (IL-12(-)IL-10(+)CCL1(+)iNOS(-)cells). Group-3 CD14(+) cells showed M1M phi polarization after treatment with CCL1 antisense oligodeoxynucleotide (ODN). Therefore, our study indicates that anti-HCC defenses of group-3 HCC chimeras are improved after CCL1 antisense ODN treatment.