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Correlation of Circulating CD64⁺/CD163⁺ Monocyte Ratio and stroma/peri-tumoral CD163⁺ Monocyte Density with Human Papillomavirus Infected Cervical Lesion Severity.

ABSTRACT: 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 CD14⁺CD16⁺ and CD14⁺CD163⁺ monocytes were elevated in No-SIL and cervical lesions. Interestingly, CD14⁺CD64⁺ 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.

SUBMITTER: Swangphon P

PROVIDER: S-EPMC5750203 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Correlation of Circulating CD64+/CD163+ Monocyte Ratio and stroma/peri-tumoral CD163+ Monocyte Density with Human Papillomavirus Infected Cervical Lesion Severity.

Swangphon Piyawut P Pientong Chamsai C Sunthamala Nuchsupha N Bumrungthai Sureewan S Azuma Miyuki M Kleebkaow Pilaiwan P Tangsiriwatthana Thumwadee T Sangkomkamhang Ussanee U Kongyingyoes Bunkerd B Ekalaksananan Tipaya T

Cancer microenvironment : official journal of the International Cancer Microenvironment Society 20171024 1-3

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 cervica ...[more]

PMID: 29064053

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Project description:Breast cancers display a high degree of diversity between and within tumors due to variations in both tumor cells and non-malignant cells of the tumor microenvironment (TME). While most studies on the TME have focused on stroma located within the tumor mass, few studies have examined the peri-tumoral microenvironment, which extends beyond the tumor margins and includes the surrounding, benign-appearing tissues. Here, we examined the heterogeneity in tumors and peri-tumoral stroma from 10 ER+PR+HER2- invasive breast carcinomas, through multi-region transcriptomic profiling. Tumor samples were obtained from the center, superior, inferior, medial, and lateral (C, S, Inf, M, L) regions of each tumor. Peritumoral samples were obtained from four radial directions corresponding to the regions the tumor samples were collected from (S, Inf, M, L) and from three zones of increasing distances from the tumor margins (Zone 1: 1-3 cm, Zone 2: 3-5 cm, Zone 3: 5-7 cm). To represent the normal breast transcriptomic state, 5 non-directional samples were each obtained from 3 non-tumor bearing breasts (NTB) - 1 patient had undergone cosmetic reduction mammoplasty and 2 patients were germline BRCA2-mutation carriers who had undergone risk-reducing mammoplasties. Total RNA was isolated and microarray was performed using the human Clariom™ S Assay (ThermoFisher Scientific). In total, 144 transcriptomic profiles (47 Tumor, 82 peri-tumoral stroma, 15 NTB) were analyzed. Heterogeneity was observed both within and between the tumor samples, highlighting that unlike the histological classification, an individual tumor is often comprised of several molecular sub-types. Similarly, the peri-tumoral stroma was also heterogeneous, albeit independent of the tumor heterogeneity. Four distinct stromal clusters were noted, which differed in their molecular pathways and cell type composition. Among these, the adipose-enriched stroma that had inflammatory cancer-associated fibroblasts and innate immune cells was significantly associated with poorer overall survival, in contrast to the myofibroblast-enriched stroma. These data together suggest that the peri-tumoral heterogeneity may be an important determinant of the evolution and treatment of breast cancers.

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Dataset Information

Correlation of Circulating CD64⁺/CD163⁺ Monocyte Ratio and stroma/peri-tumoral CD163⁺ Monocyte Density with Human Papillomavirus Infected Cervical Lesion Severity.

Publications

Correlation of Circulating CD64<sup>+</sup>/CD163<sup>+</sup> Monocyte Ratio and stroma/peri-tumoral CD163<sup>+</sup> Monocyte Density with Human Papillomavirus Infected Cervical Lesion Severity.

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