Different Distribution And Clinical Significance Of Immune T Cell Subsets In Circulation And Local Tumor Microenvironment Of Patients With Early Cervical Cancer

Background and Purpose:High-risk types of human papillomavirus are the causative agents for cervical carcinogenesis. Regulatory T cells (Treg cells) characterized by CD4+CD25highCD127low have been shown to be involved in virus-induced persistent infection. Treg cells are found to be increased in peripheral blood and tumor microenvironment of patients with solid tumors. The aim of this study is to compare the percentage of Treg cells in the peripheral blood among cervical cancers and its precursors. Methods:Peripheral blood was collected from 61 patients with cervical squamous cell carcinomas (SCC),8 patients with cervical adenocarcinomas (ADC),41 patients with high-grade cervical intraepithelial neoplasia (CIN) and 17 normal controls (NLM). Flow cytometry was employed to measure the percentage of CD4+CD25highCD127low Treg cells among CD4+ T cells in peripheral blood. The percentage of Treg cells were compared among groups using one-way ANOVA and t-test. Results:The percentage of Treg cells among CD4+T cells in the peripheral blood (mean±SD) was 10.73±2.88%,10.31±2.45%, 9.20±2.28% and 7.88±1.18% in ADC cases, SCC cases, CIN cases and normal controls, respectively (P=0.001). Among squamous lesions, the percentage of Treg cells was elevated and correlated with the severity of the disease (SCC>CIN>NLM, P<0.001). The percentage of Treg cells were higher in ADC cases compared to SCC cases, however, there was no statistic significance (P=0.657). Among the 69 invasive carcinomas, the mean age was 47.8 years old (29-70). Thirty-two and 37 patients were diagnosed as stage Ⅰ and stage Ⅱ, respectively (FIGO staging 2009). Seventeen (24.6%) patients had pelvic lymph node metastasis. There was a trend that advanced cases had more Treg cells in their peripheral blood, however, no statistical difference was found between the percentage of Treg cells and any chnicopathologic parameters, such as FIGO stage (Ⅱ vs Ⅰ:10.67±2.67% vs 10.00±2.24%, P=0.266), tumor size (>4 cm vs≤ cm:10.68±2.31% vs 10.04±2.63%, P=0.284) and lymph node metastasis (positive vs negative:11.06±2.56% vs 10.13±2.44%, P=0.181). Conclusion:The percentage of Treg cells in peripheral blood were increased in patients with cervical intraepithelial neoplasia and cervical cancers, which indicated that Treg cells might play a critical role in malignant transformation of cervical intraepithelium. However, their significance in the progression of invasive carcinomas warrants further study.Background and Purposes:The purpose of this study is to compare the systemic and intratumor T-cell compartment in patients with early-stage cervical carcinomas. Methods:Multi-Parametric flow cytometry was employed to characterize T cell subpopulations (CD4+, CD8+ and Treg) in peripheral blood from 46 patients with early-stage squamous cell carcinomas and normal controls. T cell subpopulations were also detected in primary tumors from 38 patients with early-stage squamous cell carcinomas. The percentage of T cells and their subpopulations (naive, memory and effector) were enumerated and compared. Results:The percentage of the circulating CD4+ T-cells in cervical cancer patients was significantly higher than that in normal controls(58.20±9.37% vs 52.49±7.09%, P<0.05). While the percentage of the circulating CD8+ T-cells in cervical cancer patients was significantly lower than that in normal controls(29.18±8.00% vs 34.11±7.11%, P<0.05). In primary tumors, effector memory T-cells (Tem) were the predominant subpopulation among the CD4+ T-cells (83.83±.25%) and CD8+ T-cells (88.31±9.36%), significantly higher than their counterparts in peripheral blood (29.28±14.02% and 35.82±14.71% respectively, P<0.05). The naive T-cells among intratumoral CD4+ T-cells and CD8+T-cells were 1.30±1.89% and 1.24±1.38% respectively, significantly lower than their counterparts in peripheral blood (32.40±15.07% and 27.91±17.73%, respectively, P<0.05). In primary tumors, the percentage of the CD4+T-cell was inversely associated with lymph vascular invasion, deep myometrial invasion and lymph node metastasis; the percentage of the CD8+ T-cell and CD8+ Tern cells were reversely associated with lymphvascular invasion, stromal myometrial invasion and lymph node metastasis. The percentages of the circulating Treg cells and Helios+ Treg cells were 7.51±1.92% and 66.12±13.16% respectively, significantly increased when compared with their percentages in normal controls(6.16±1.89%,50.79±10.59%, P<0.05, respectively). In primary tumors, the percentage of terminal effector Treg cells among CD4+ T cells was significantly higher than that in peripheral blood (43.91±21.17% vs 6.15±9.08%, P<0.05); while the percentage of naive Treg cells was significantly lower than that in peripheral blood (0.45±0.32% vs 19.89±.77%, P<0.05). The number of the circulating CD4+Foxp3+ Treg cells was inversely associated with lymph vascular invasion and lymph node metastasis. Conclusions:In early-stage cervical cancer, subpopulations of the CD4+, CD8+ T-cells and Treg cells are differently distributed in circulation and primary tumor. Increasing of CD4+Foxp3+ Treg cells in peripheral blood and decreasing of intratumoral CD8+ T-cell and CD8+ Tern cells are correlated with tumor invasive and metastatic Phenotype which implicate an important role of different T cell subpopulations in the generation and regulation of antitumor immunity.