Proportion of CD4+CD25+ regulatory T lymphocyte in peripheral blood of patients with gynecologic cancer

Ma, Jin Young; Kim, Yong Man; Jung, Min Hyung; Song, Ha Young; Kim, Dae Yeon; Kim, Jong Hyeok; Kim, Young Tak; Nam, Joo Hyun; Mok, Jung Eun

Abstract

OBJECTIVE
Recently the existence of a CD4+CD25+ regulatory (Treg) population has been described in rodents and humans. It is unclear how the immune response cells interact to tumor cells effectively, but the malignant tumor cell growth was suppressed by the main effect of T lymphocytes and natural killer cells in experimental studies using various biologic response modifier. This study was performed to investigate the proportion of CD4+CD25high Tregs and expression of Foxp3 in Peripheral blood (PBL)s in patients with cervical, ovarian or uterine cancers.
METHODS
Blood samples were collected from 10 healthy women and a total of 40 patients with gynecologic cancer at department of Obstetrics and Gynecology, Asan Medical Center, Seoul, Korea, from March 2005 to September 2005, were enrolled in study group. Information regarding patient history and tumor stage was recorded. They were diagnosed at same center at first, and never been treated any therapy. The population of CD4+CD25+high Tregs as a percentage of total CD4+cells was evaluated by flow cytometric analysis. We measured the proportion of Treg cell that co-express CD4 and CD25 in the peripheral blood lymphocytes form patients with either cervical, ovarian uterine cancer or carcinoma in situ of cervix. Expression of Foxp3 in the CD4+subsets defined by electrophoresis.
RESULTS
The following tumor entities were included cervical cancer (n=10. 7 in stage I, 1 in stage II, 1 in stage III, 1 in stage IV); ovarian cancer (n=10. 4 in stage I, 0 in stage II, 5 in stage III, 1 in stage IV), ; uterine cancer (n=10. 9 in stage I, 0 in stage II, 0 in stage III, 1 in stage IV). In cervical cancer patient, ovarian cancer patients, uterine cancer patients and healthy women, the proportion of CD4+CD25high Tregs was 4.53% (SD 2.30), 6.89% (SD 7.81), 4.37% (SD 2.43) and 0.87% (SD 0.57) of the total CD4+cells respectively. The proportion of CD4+CD25+high T cells was significantly higher in cervical cancer patients (p=0.016), ovarian cancer patients (p=0.001) and uterine cancer patients (p=0.038) when compared with healthy women. But there was no significant difference in proportion of CD4+CD25+ Tregs comparing with healthy women. Expression of Foxp3 was significantly thicker in tumor-associated lymphocytes than control T cells by electrophoresis.
CONCLUSION
In conclusion, our data suggested that the increase in frequency of regulatory T cells might play a role in modulation of the immune response against cervical, ovarian, uterine cancer could be important in design of immunotherapeutic approaches.