Swangphon Piyawut, Pientong Chamsai, Sunthamala Nuchsupha, Bumrungthai Sureewan, Azuma Miyuki, Kleebkaow Pilaiwan, Tangsiriwatthana Thumwadee, Sangkomkamhang Ussanee, Kongyingyoes Bunkerd, Ekalaksananan Tipaya
Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand.
HPV & EBV and Carcinogenesis Research Group, Khon Kaen University, Khon Kaen, 40002, Thailand.
Cancer Microenviron. 2017 Dec;10(1-3):77-85. doi: 10.1007/s12307-017-0200-2. Epub 2017 Oct 24.
HPV infected cervical cells secrete mediators that are gradually changed and have influence on infiltrating M2 phenotypic monocytes in cervical lesions. However, profiles of circulating immune cells in women with cervical lesions and M2 phenotypic monocyte activity in HPV infected cervical lesions are limited. This study aimed to investigate circulating monocyte populations correlated with M2 phenotype density and its activity in HPV infected cervical lesions. HPV DNA was investigated in cervical tissues using PCR. High risk HPV E6/E7 mRNA was detected using in situ hybridization. CD163 immunohistochemical staining was performed for M2 macrophage. CD163 and Arg1 mRNA expression were detected using real-time PCR. Circulating monocyte subpopulations were analyzed using flow cytometry. CD163 and Arg1 mRNA expression were increased according to cervical lesion severity and corresponding with density of M2 macrophage in HSIL and SCC in stroma and peri-tumoral areas. Additionally, the relationship between M2 macrophage infiltration and high risk HPV E6/E7 mRNA expression was found and corresponded with cervical lesion severity. Circulating CD14CD16 and CD14CD163 monocytes were elevated in No-SIL and cervical lesions. Interestingly, CD14CD64 monocyte was greatly elevated in HSIL and SCC, whereas intracellular IL-10 monocytes were not significantly different between cervical lesions. The correlation between increasing ratio of circulating CD64/CD163 monocyte and density of infiltrating CD163 monocytes was associated with severity of HPV infected cervical lesions. The elevated circulating CD64/CD163 monocyte ratio correlates to severity of HPV infected cervical lesions and might be a prognostic marker in cervical cancer progression.
人乳头瘤病毒（HPV）感染的宫颈细胞会分泌一些介质，这些介质会逐渐发生变化，并对宫颈病变中浸润的M2表型单核细胞产生影响。然而，宫颈病变女性循环免疫细胞的特征以及HPV感染的宫颈病变中M2表型单核细胞的活性研究有限。本研究旨在调查与HPV感染的宫颈病变中M2表型密度及其活性相关的循环单核细胞群体。采用聚合酶链反应（PCR）检测宫颈组织中的HPV DNA。采用原位杂交检测高危型HPV E6/E7 mRNA。对M2巨噬细胞进行CD163免疫组织化学染色。采用实时荧光定量PCR检测CD163和精氨酸酶1（Arg1）mRNA表达。采用流式细胞术分析循环单核细胞亚群。CD163和Arg1 mRNA表达随着宫颈病变严重程度增加而升高，且与高级别鳞状上皮内病变（HSIL）和基质及肿瘤周边区域鳞状细胞癌（SCC）中M2巨噬细胞密度相对应。此外，发现M2巨噬细胞浸润与高危型HPV E6/E7 mRNA表达之间的关系，并与宫颈病变严重程度相对应。在无上皮内病变（No-SIL）和宫颈病变中，循环CD14⁺CD16⁻和CD14⁺CD163⁺单核细胞升高。有趣的是，CD14⁺CD64⁺单核细胞在HSIL和SCC中显著升高，而细胞内白细胞介素-10（IL-10）单核细胞在宫颈病变之间无显著差异。循环CD64⁺/CD163⁺单核细胞增加比例与浸润性CD163⁺单核细胞密度之间的相关性与HPV感染的宫颈病变严重程度相关。循环CD64⁺/CD163⁺单核细胞比例升高与HPV感染的宫颈病变严重程度相关，可能是宫颈癌进展的一个预后标志物。
