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Publications (3)4.54 Total impact

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    ABSTRACT: Adoptive cell transfer (ACT) immunotherapy has been used clinically for years to treat malignancies. Improving the killing efficiency of effector cells, such as tumor-specific cytotoxic T lymphocytes (CTLs), is an important component for enhancing the clinical response of cancer immunotherapy. Hence, we explored a novel method for preparing cancer-specific CTLs using naive T lymphocytes. C57BL/6 mice bearing B16 melanoma tumors were pretreated with cyclophosphamide (CTX) by peritoneal injection. The immunosuppressive influence of CTX on tumor regression and the tumor microenvironment was assessed. Naive T cells and T cell pools were isolated via negative selection using immunomagnetic beads. The proliferative potential and cytokine production of different T cell subpopulations were evaluated in vitro. Tumor-specific CTLs derived from naive T cells (naive CD4+ T cells: naive CD8+ T cells = 2:1) and pooled T cells were generated in vitro, respectively. B16 melanoma-bearing C57BL/6 mice were pretreated with CTX, followed by ACT immunotherapy using dendritic cell-induced CTLs. The homing abilities of the effector cells and interleukin-2 (IL-2), interferon-γ, granzyme B, and perforin mRNA levels in tumor tissues were evaluated, and the change in tumor volume was measured. Mice receiving CTX peritoneal pretreatment injections did not display tumor regression compared with control mice. However, a significant downregulation of splenic Tregs and tumor growth factor-β1 (TGF-β1) and interleukin-10 (IL-10) serum levels was observed (P < 0.05). Naive T cells showed a stronger proliferative capacity and elevated cytokine production than did pooled T cells (P < 0.05). In addition, effector cells generated from naive T cells displayed more potent antitumor activity in vivo than those derived from pooled T cells (P < 0.05). Effector cells derived from the naive T cells possess a stronger proliferative potential, homing capacity, and enhanced cytokine production, which leads to a superior antitumor response.
    Chinese medical journal 04/2014; 127(7):1328-33. · 0.90 Impact Factor
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    ABSTRACT: Adoptive cell transfer immunotherapy of malignant tumors has the problem of symbiosis between effector cells and tumor cells, a short in vivo residence time, and a poor killing efficiency of effector cells. Thus, releasing effector cells from the cancer immunosuppressive microenvironment and improving their effective time and functional status in vivo would seem to be ideal strategies for facilitating immunotherapy. Low-dose cyclophosphamide administration can effectively break immunotolerance by inhibiting regulatory T cells. In the present study, in order to verify whether the persistence, distribution and function of effector cells can be improved by inhibiting immunosuppressive microenvironment, low-dose cyclophosphamide was previously intraperitoneally injected into melanoma-bearing C57BL/6 mice, thereafter, CFSE-labeled cytotoxic T lymphocytes were transfused intravenously, and their effective time, distributive pattern, and killing efficiency in different groups were observed by measuring the fluorescence intensity and cell cycle of cytotoxic T lymphocytes distributed in various organs, in comparison with tumor growth. We found down-regulating Tregs in vivo can simultaneously reduce the levels of interleukin-10 and transforming growth factor-β. Migration and distribution of cytotoxic T lymphocytes in vivo was found to vary with time. Inhibition of immunotolerance can significantly improve the persistence, distribution, and function of cytotoxic T lymphocytes. Correspondingly, significantly higher secretion of perforin, granzyme B, IL-2, and IFN-γ in tumor tissues with decreased tumor growth was seen in the cyclophosphamide injection group than in the control group. Our study may provide useful information on the cyclophosphamide-mediated mechanism for facilitating tumor immunotherapy by inhibiting the immunosuppressive tumor microenvironment. This article is protected by copyright. All rights reserved.
    Scandinavian Journal of Immunology 05/2013; · 2.20 Impact Factor
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    ABSTRACT: Epidermal growth factor (EGF) plays an important role in tumorigenesis. The association between the +61 A/G polymorphism of the EGF gene and colon cancer risk remains controversial and unclear. The objective of this study was to investigate the association between EGF +61 A/G polymorphism and colon cancer risk in a Chinese population. A hospital-based case-control study was conducted to assess the possible association between EGF +61 A/G polymorphism and colon cancer risk. A total of 180 colon cancer patients and 180 cancer-free healthy controls were recruited in the Chinese population. Genomic DNA was isolated from peripheral blood, and gene polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Colon cancer patients had a significantly higher frequency of +61 GG genotype (odds ratio [OR]=1.93, 95% confidence interval [CI]=1.07, 3.50; p=0.03) than that of controls. When stratified by the tumor location, tumor size, growth pattern, differentiation, and tumor-node-metastasis (TNM) stage of colon cancer, no statistically significant results were observed. Our study revealed that EGF +61 GG genotype was associated with a higher risk of colon cancer in Chinese population.
    Genetic Testing and Molecular Biomarkers 05/2012; 16(9):1142-5. · 1.44 Impact Factor