PT - JOURNAL ARTICLE AU - WADA, JUNJI AU - YAMASAKI, AKIO AU - NAGAI, SHUNTARO AU - YANAI, KOUSUKE AU - FUCHINO, KOUTA AU - KAMEDA, CHIZU AU - TANAKA, HARUO AU - KOGA, KENICHIRO AU - NAKASHIMA, HIROSHI AU - NAKAMURA, MASAFUMI AU - TANAKA, MASAO AU - KATANO, MITSUO AU - MORISAKI, TAKASHI TI - Regulatory T-Cells Are Possible Effect Prediction Markers of Immunotherapy for Cancer Patients DP - 2008 Jul 01 TA - Anticancer Research PG - 2401--2408 VI - 28 IP - 4C 4099 - http://ar.iiarjournals.org/content/28/4C/2401.short 4100 - http://ar.iiarjournals.org/content/28/4C/2401.full SO - Anticancer Res2008 Jul 01; 28 AB - We previously showed that a combination therapy with tumor cell-pulsed monocyte-derived dendritic cells (DCs) and activated lymphocytes was well tolerated in patients with disseminated carcinomas. Recently, accumulating evidence has indicated that regulatory T-cells (Tregs), a unique population of CD4+ T-cells, are increased in patients with several advanced malignancies and prevent cell-mediated immune responses against tumors. However, reports analyzing the relationship between the Tregs population and the effects of immunotherapy are extremely rare. In the present study, 22 patients received an intravenous injection of DC-activated lymphocytes (DAK) and/or a subcutaneous injection of tumor-pulsed DCs (DC vaccine) every 2 to 4 weeks. The Tregs were defined based on their expression of CD4, CD25 and FOXP3, a transcription factor. Most CD4+CD25high T-cells expressed FOXP3. Therefore, CD4+CD25high T-cells were evaluated as Tregs in the present study. As reported previously, the percentage of Tregs (% Tregs) among total CD4+ T-cells in peripheral blood mononuclear cells (PBMCs) was significantly higher for advanced cancer patients than for healthy volunteers. When the patients were divided into three groups according to their survival time, i.e. 12 short-survival patients, 4 medium-survival patients and 6 long-survival patients, the % Tregs of the long-survival patients before the therapy was significantly lower than that of the short-survival patients (p=0.026). The % Tregs decreased after the therapy, although the difference did not reach statistical significance. When the patients were divided into a high group (>4.99% : 7 patients) and a low group (<4.99% : 15 patients) according to their % Tregs before the therapy, the survival times of the two groups differed significantly (p=0.0034). These data suggest that the % Tregs among the PBMCs might be used as an effect prediction factor of immunotherapy for patients with advanced cancer. Copyright© 2008 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved