CD33^(low)CD11b^(low)髓系细胞在肝癌患者中的表型、形态与功能

Phenotype, morphology and function of hepatocellular carcinoma-associated CD33^(low)CD11b^(low) myeloid cells in hepatocellular carcinoma patients

目的探讨在肝癌患者外周血和肿瘤组织标本中CD33^(low)CD11b^(low)髓系细胞的表型、形态与功能。方法分别采用流式细胞仪和Wright-Giemsa染色法检测肝癌患者外周血和肿瘤组织标本中CD33^(low)CD11b^(low)细胞的表型和核型,并比较其在健康人和肝癌患者外周血以及肝癌组织中的丰度变化。分选该群细胞与同源T细胞共培养以检测其免疫学功能。结果在肝癌患者外周血和肿瘤中的粒细胞,除经典的CD33^(low)CD11b^(high)中性粒细胞外,还存在一群CD33^(low)CD11b^(low)类嗜碱性粒细胞(不表达CD15、CD16和CD66b,高表达CD123、CD38,低表达HLA-DR)。CD33^(low)CD11b^(low)细胞在肝癌患者外周血中比例高于健康人,在肿瘤组织中比例高于癌旁正常组织,且主要呈现未成熟粒细胞的核型(P<0.001)。从肝癌组织中分离得到的CD33^(low)CD11b^(low)细胞具有促进T细胞增殖的能力,而健康人外周血CD33^(low)CD11b^(low)细胞经肿瘤培养上清处理后也具有更强的促进T细胞增殖的能力。结论 CD33^(low) CD11b^(low)细胞在表型上与嗜碱性粒细胞基本相符,在肝癌患者中多数呈现未成熟粒细胞的核型。肿瘤微环境可激活CD33^(low)CD11b^(low)细胞的促免疫反应功能。

Objective To investigate the phenotype, morphology, and function of CD33lowCD11blow myeloid cells in the patients with hepatocellular carcinoma （HCC）. Methods The phenotype and morphology of CD33lowCD11blow myeloid cells were examined using flow cytometry and Wright-Giemsa staining. The immune functions of CD33lowCD11blow myeloid cells were tested via T cell co-culture assay, using freshly isolated CD33lowCD11blow myeloid cells from HCC tissues or tumor supernatant-treated blood CD33lowCD11blow myeloid cells from healthy donors. Results Aside from canonical polymorphonuclear neutrophils, there was a subset of CD33lowCD11blow granuloeytes in the peripheral blood and tumor tissues in the HCC patients. These cells expressed CD123, CD38 and a low level of HLA-DR, but not CD15, CD16, or CD66b, which resembled a phenotype of basophils. Interestingly, these cells exhibited an immature morphology in HCC patients （P 〈 0. 001 ）. The frequencies of blood CD33lowCD11blow myeloid cells were significantly higher in the HCC patients than the healthy donors, and these cells were enriched in the tumors. HCC-conditioned CD33lowCD11blow myeloid cells had profound capacity in fostering T cell proliferation. Conclusion CD33lowCD11blow myeloid cells, a subset of myeloid cells phenotypically resembled basophils,accumulate in the HCC patients and exhibit an immature morphology, which may contribute to anti-tumor immune response in the tumor microenvironment.