Vaccination of B-CLL patients with autologous dendritic cells can change the frequency of leukemia antigen-specific CD8+ T cells as well as CD4+CD25+FoxP3+ regulatory T cells toward an antileukemia response.

Recently, we described that vaccination with allogeneic dendritic cells (DCs) pulsed with tumor cell lysate generated specific CD8+ T cell response in patients with B-cell chronic lymphocytic leukemia (B-CLL). In the present study, the potential of autologous DCs pulsed ex vivo with tumor cell lysates to stimulate antitumor immunity in patients with B-CLL in early stages was evaluated. Twelve patients at clinical stage 0-2 as per Rai were vaccinated intradermally up to eight times with a mean number of 7.4 x 10(6) DCs pulsed with B-CLL cell lysate. We observed a decrease of peripheral blood leukocytes and CD19+/CD5+ leukemic cells in five patients, three patients showed a stable disease and four patients progressed despite DC vaccination. A significant increase of specific cytotoxic CD8+ T lymphocytes against the leukemia-associated antigens RHAMM or fibromodulin was detected in four patients after DC vaccination. In patients with a clinical response, an increase of interleukin 12 (IL-12) serum levels and a decrease of the frequency of CD4+CD25(+)FOXP3+ T regulatory cells were observed. Taken together, the study demonstrated that vaccination with autologous DC in CLL patients is feasible and safe. Immunological and to some extend hematological responses could be noted, justifying further investigation on this immunotherapeutical approach.

Myeloid and lymphoid dendritic cells and cytotoxic T lymphocytes in peripheral blood of non-small cell lung cancer patient--a pilot study.

PURPOSE: Dendritic cells (DCs) and cytotoxic T lymphocytes (CTLs) are the first protecting barrier against different pathogens (viruses, bacteria and neoplasms cells). Immature myeloid- and lymphoid dendritic cells possess ability to phagocytose and present antigens to lymphocytes. They have also ability to produce IL-12, which is also known as natural killer cell stimulatory factor or cytototoxic lymphocyte maturation factor. The aim of the study was to demonstrate the relationship between percentage of immature dendritic cells and percentage of CTLs subtypes in peripheral blood of non-small cell lung cancer (NSCLC). MATERIAL AND METHODS: The study population consisted of 10 patients suffered from NSCLC (the mean age: 61.8 +/- 10.55). The monoclonal antibodies and three-color flow cytometry technique was applied to determine the cells phenotype in peripheral blood. RESULTS: Significant negative correlation (R = -0.693, p < 0.05) between percentage of lymphoid DCs and percentage of CTLs was shown. The myeloid to lymphoid DCs ratio significantly positively (R = +0.638, p < 0.05) correlated with the percentage of CTLs. The significant negative correlation between the percentage of myeloid DCs and the percentage of CTLs-IL-12R-positive cells, as well as expression of this receptor were also ascertained (R = -0.68, p < 0.05 and R = -0.757, p < 0.01, respectively). CONCLUSIONS: In presented pilot study we demonstrated clearly relationship between the percentage of immature DCs and the percentage and the phenotype of CTLs in peripheral blood of lung cancer patients.

Allogeneic dendritic cells pulsed with tumor lysates or apoptotic bodies as immunotherapy for patients with early-stage B-cell chronic lymphocytic leukemia.

Recently, immunotherapies with allogeneic dendritic cells (DCs) pulsed with tumor antigens to generate specific T-cell responses have been tested in clinical trials for patients with solid tumors. This is the first report on a clinical vaccination study with DCs for patients with B-cell chronic lymphocytic leukemia (B-CLL). The potential of allogeneic DCs pulsed ex vivo with tumor cell lysates or apoptotic bodies to stimulate antitumor immunity in patients with B-CLL in early stages was evaluated. Monocyte-derived DCs were obtained from unrelated healthy donors. Nine patients (clinical stage 0 and 1 according to Rai) were vaccinated five times with a mean number of 32 x 10(6) stimulated DCs administered intradermally once every 2-3 weeks. No signs of autoimmunity were detected, and only mild local skin reactions were noted. During the treatment period, we observed a decrease of peripheral blood leukocytes and CD19+/CD5+ leukemic cells. In one patient, a significant increase of specific cytotoxic T lymphocytes against RHAMM/CD168, a recently characterized leukemia-associated antigen, could be detected after DC vaccination. Taken together, the study demonstrated that DC vaccination in CLL patients is feasible and safe. Immunological and to some extent hematological responses could be noted, justifying further investigation on this immuno-therapeutical approach.

Blood myeloid and lymphoid dendritic cells are stable during the menstrual cycle but deficient during mid-gestation.

The aim of this study was to estimate the populations of peripheral blood myeloid and lymphoid dendritic cells (CD1c(+), BDCA-2(+), BDCA-4(+)) and the CD1c(+):BDCA-2(+) ratio in phases of the ovarian cycle and in normal pregnant patients. 18 non-pregnant women and 17 normal pregnant women were included. Dendritic cells were isolated from peripheral blood, stained with monoclonal antibodies (mAbs) against blood dendritic cell antigens (anti-BDCA-1, BDCA-2, BDCA-4) and estimated using flow cytometry. CD1c(+), BDCA-2(+) and BDCA-4(+) dendritic cells were present in the follicular and luteal phases of the ovarian cycle and in all trimesters of normal pregnancy. The percentages of CD1c(+) dendritic cells did not differ between the follicular and luteal phases of the ovarian cycle. The percentage of BDCA-2(+) dendritic cells was lower in the luteal phase of the ovarian cycle compared with the follicular phase, but the differences were not statistically significant. The CD1c(+):BDCA-2(+) cell ratio was significantly lower in the luteal phase compared with the follicular phase of the ovarian cycle. The numbers of dendritic cells were significantly lower in the second trimester when compared with the first and third trimesters of normal pregnancy. Furthermore, in the second trimester, the CD1c(+):BDCA-2(+) ratio was higher than in the other trimesters of normal pregnancy. All populations of dendritic cells and the CD1c(+):BDCA-2(+) ratio did not differ in the first and third trimesters of physiological pregnancy. Our results suggest that myeloid and lymphoid dendritic cells are not affected by steroid hormones during the menstrual cycle. The deficiency of peripheral blood dendritic cells observed during the second trimester of normal pregnancy can be associated with their migration to the uterus during the second physiological invasion by cytotrophoblast.

Myeloid and lymphoid dendritic cells in normal pregnancy and pre-eclampsia.

The aim of our study was to estimate the populations of peripheral blood myeloid and lymphoid dendritic cells (CD1c+, BDCA-2+) and the CD1c+ : BDCA-2+ ratio in normal pregnant women and in patients with pre-eclampsia. Fifteen women in the first, second and third trimesters of normal pregnancy, and 25 patients with pre-eclampsia were included in the study. The dendritic cells were isolated from peripheral blood, stained with monoclonal antibodies against blood dendritic cell antigens (anti-CD1c, anti-BDCA-2) and estimated using the flow cytometric method. CD1c+ and BDCA-2+ dendritic cells were present in women during all trimesters of physiological pregnancy and in pre-eclamptic patients. It was observed that the numbers of dendritic cells were significantly lower in the second trimester when compared with the first and third trimesters of normal pregnancy. Furthermore, in the second trimester, CD1c+ : BDCA-2+ ratio was higher than in the other trimesters of physiological pregnancy. All populations of dendritic cells and CD1c+ : BDCA-2+ ratio did not differ in the first and third trimesters of normal pregnancy. The percentage of BDCA-2+ dendritic cells was significantly lower in pre-eclampsia in comparison with healthy women in the third trimester of physiological pregnancy, while CD1c+ : BDCA-2+ ratio was significantly higher in pre-eclamptic patients when compared with control groups. We concluded that dendritic cells may be involved in the immune regulation during physiological pregnancy. CD1c+ and BDCA-2+ cells can influence the Th2 phenomenon which is observed during physiological pregnancy. Furthermore, it seems possible that lower BDCA-2+ cells percentage and higher CD1c+ : BDCA-2+ ratio can be associated with increased Th1-type immunity in patients with pre-eclampsia.