Detection And Significance Of T Lymphocyte Subsets In Cervical Cancer Tissue

Background and ObjectiveCervical cancer is a public health problem and one of the main causes of the death of women's cancer in all over the world, there is an increasing trend of morbidity and mortality in recent years. Recently, a lot of data indicate that cervical cancer is closely related to human papillomavirus (HPV), but most people of HPV infection can clear the virus in 12-30months.So, in addition to HPV infection, cervical cancer is also related to other factors, especially the organism immune state. The immune plays a crucial role in continuously infected HPV and integration virus gene, it even can induces the cervical cancer. T lymphocyte subsets are important antitumor effect cells, these cells including CD4+T and CD8+T lymphocyte and CD4+CD25+FOXP3+regulate T cell (Treg). In normal condition, there is a certain ratio between T cell subsets, this can maintain the symmetery of cell immunity. When T cell subsets number change, the symmetery of each second cluster is broken, it will cause the mess of immunity function, and promote the occurrence and development of tumor.Formerly, the research of CD4+T,the CD8+T lymphocyte and the Treg cells mainly concentrated in cervical cancer patient's peripheral blood, but regarding their number in cervical cancer tissue and the relationship between T cell subsets and HPV were still rarely reported. In this study, we used immunohistochemical staining to detect the quantities of T cell subsets in cervical cancer, and analyzed the relationship between T cell subsets and HPV infection and the role of T cell subsets in the development of cervical cancer.Materials and Methods1. The paraffin-embedded tissues of 179 cases of cervical lesions we were collected included 25 cases of cervicitis, 17 cases of low grade CIN (CIN1), 41 cases of high grade CIN (included 16 cases of CIN2 and 25 cases of CIN3), 67 cases of cervical squamous cell carcinoma (SCC) and 29 cases of cervical adenocarcinoma(ADC).2. HPV DNA-chips technology was used to detect HPV genotyping in all cases.3. CD4+T, CD8+T and FOXP3+T lymphocytes were detected by immunohistochemistry.Results1. The number of CD4+T lymphocytes was 115.20±5.59 in cervicitis group, 107.80±5.53 in low grade CIN, 92.90±12.67 in high grade CIN, 87.10±5.10 in SCC and 79.70±5.85 in ADC. The number of CD4+T lymphocytes in cervicitis and low grade CIN group was significantly higher than high grade CIN, SCC and ADC(P<0.05); the number in high grade CIN was higher than that in SCC and ADC (P <0.05).2. The number of CD8+T lymphocytes was 59.50±5.26 in cervicitis, 56.30±6.04 in low grade CIN, 70.30±4.65 in high grade CIN, 84.10±3.07 in SCC and 80.50±6.79 in ADC. The number of CD8+T lymphocytes in SCC and ADC was significantly higher than high grade CIN, low grade CIN and cerviciti(sP<0.05); the number in high grade CIN was higher than that in cervicitis and low grade CIN (P <0.05).3. From cervicitis, low grade CIN, high grade CIN to cervical cancer, the number of CD4+T lymphocytes gradually reduce but CD8+T lymphocytes gradually increase, this cause the ratio of CD4~+T /CD8~+T decreased gradually. 4. The number of FOXP3~+T lymphocytes was 4.64±4.62 in cervicitis, 6.12±5.23 in low grade CIN, 18.15±19.63 in high grade CIN, 60.03±28.72 in SCC, 27.17±14.08 in ADC. The number of FOXP3~+T lymphocytes in SCC was significantly higher than that in ADC, high grade CIN, low grade CIN and cervicitis(P<0.05); the number in ADC and high grade CIN was higher than that in cervicitis and low grade CIN groups(P <0.05).From cervicitis, low grade CIN, high grade CIN to SCC, the number of FOXP3~+T lymphocytes has an increasing trend.5. The results of HPV genotype in cervical lesions: in 179 cases, there were 138 cases of HPV-positive and 41 cases of HPV-negative, HPV infection ratioleaded up to 77.09%. High -risk HPV16 with 59 cases was the most predominant type; HPV18 was in the second place with 25 cases; the rest was the infection by other types with 33 cases (includedHPV11,31,33,35,42,45,51, 52,56,58, 59, 66); and there were 21cases of mixed infection (included HPV6.16;11.16;16.18; 16.31; 16.33;16.52;16.58;16.59;16.68; 18.16; 31.58; 52.33; 58.6; 16.33.59)6. There was a certain relationship between T lymphocyte subsets and HPV infection. In HPV-positive cases, there were 74.89±10.30 and 38.69±31.25 cells per high power field of CD8~+T lymphocytes and FOXP3~+T lymphocytes, which were higher than 60.94±7.52 and 10.61±14.91 in HPV-negative cases (P<0.05). The number of CD4~+T lymphocytes was 90.19±13.50 in HPV-positive cases, lower than HPV-negative cases (P<0.05). There were some differences in the number of FOXP3~+T lymphocytes with different HPV type, the number of FOXP3~+T lymphocytes in HPV16 was 48.32±30.31, significantly higher than that in mixed infection, HPV18 and other type infection. Conclusions1. Compared to cervicitis, low grade CIN and high grade CIN, the number of CD4~+T lymphocytes decrease but CD8~+T lymphocytes increase in cervical cancer tissue. From cervicitis, low grade CIN and high grade CIN to cervical cancer,CD4~+T lymphocytes reduce gradually and CD8~+T lymphocytes increase gradually, and the ratio of CD4~+T /CD8~+T decrease. These results suggest that along with the progress of cervical lesions, T cell subsets appear to mess and the disturbance continuously turn worse.2. FOXP3~+T lymphocytes in cervical cancer have a higher number than in cervicitis, low grade CIN and high grade CIN, and there also has an increasing trend from cervicitis, low grade CIN and high grade CIN to cervical cancer. These results reflect that Treg cells play an important role in immunosuppression.3. There is a certain relationship between T lymphocyte subsets and HPV infection, in HPV-positive cases, Treg cells and CD8~+T lymphocytes all increase but CD4~+T lymphocytes decrease. It shows that in the development process of cervical cancer, T cell subsets are interaction with HPV, may turn the disturbance of organism immunity function worse, and promote the process of disease.