期刊
ONCOIMMUNOLOGY
卷 6, 期 4, 页码 -出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/2162402X.2017.1299301
关键词
Antisense oligodexynuclotide; CCL1; hepatocellular carcinoma; host antitumor resistance; macrophage
资金
- JSPS KAKENHI [JP26860533]
- Grants-in-Aid for Scientific Research [26860533] Funding Source: KAKEN
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.
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