Regulatory T-cells are possible effect prediction markers of immunotherapy for cancer patients.

Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Anticancer research (Impact Factor: 1.83). 01/2008; 28(4C):2401-8.
Source: PubMed

ABSTRACT 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.

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    ABSTRACT: Colorectal cancer (CRC) is the third-leading cause of cancer deaths in the United States. There is a disparity in CRC cases, with blacks having a higher incidence and mortality than whites. The cause of these disparities is a mixture of socioeconomic, dietary, lifestyle, and biological factors. The role of biology in causing these disparities is largely unknown. Studies have shown that immune cell infiltration into the tumor can be used as prognostic factors in CRC and other cancers. Many of these studies focus on cytotoxic T lymphocytes, but other cells exist that possess antitumorigenic properties. One of these types of cells is natural killer (NK) cells, which are both cytotoxic and capable of secreting IFN-γ. The goal of this study is to elucidate the role of the immune response—specifically, NK cells—in the prognostic disparities observed in colon cancer based on race, gender, and infiltration of CD8+ T lymphocytes. Formalin-fixed paraffin-embedded archival colon cancer tissue slides were obtained from the North Carolina Colon Cancer Study (NCCCS), a population-based cohort (45% black, 55% white). Immunohistochemistry (IHC) was used to detect the presence of CD57+ cells, and the mean numbers of intraepithelial and intratumoral cells were quantified by two independent observers from three high-powered fields (HPF; 100x total magnification). Tumors from 126 different patients in the NCCCS, culled from the top and bottom quartiles for CD8+ cell infiltration and chosen to as equally represent blacks/whites and males/females as possible, were analyzed by IHC. The Mann-Whitney U test was employed for statistical analysis. No significant difference was found between blacks and whites using both intraepithelial and intratumoral CD57+ cell counts, but a significant difference was observed between males and females using intratumoral CD57+ cell counts (p<0.05). Additionally, a highly significant difference in CD57+ cell infiltration was found between high- and low-CD8+ cell infiltrating patients (both p<0.001). These data indicate some degree of immune coordination between CD8+ and CD57+ cells. The basis of this immune coordination depends on the identity of the CD57+ cells, but may include cytotoxic T lymphocytes and/or NK cells (either in a cytotoxic capacity or by secretion of IFN-γ). Further investigation into the identity and function of the CD57+ cell infiltrate are needed. Additionally, our data suggest—but do not completely rule out the possibility—that NK cells are not involved in the observed racial disparities in colon cancer. Furthermore, the data do not eliminate the possibility that other immunological factors are involved in contributing to the racial disparity.
    12/2011, Degree: M.S. Cell and Molecular Biology, Supervisor: Kathleen L. McGuire
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