Mechanisms underlying the synergistic effect of SU5416 and cisplatin on cytotoxicity in human ovarian tumor cells

2004 ◽  
Author(s):  
Xiaosong Zhong ◽  
Xiping Li ◽  
Gangduo Wang ◽  
Yunfeng Zhu ◽  
Guodong Hu ◽  
...  
Keyword(s):  
Synergistic Effect ◽  
Tumor Cells ◽  
Ovarian Tumor ◽  
Ovarian Tumor Cells

SV40 early genes induce neoplastic properties in serous borderline ovarian tumor cells

2008 ◽  
Vol 111 (1) ◽  
pp. 125-131 ◽  
Author(s):  
Michelle M. Woo ◽  
Clara M. Salamanca ◽  
Jaime Symowicz ◽  
M. Sharon Stack ◽  
Dianne M. Miller ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Ovarian Tumor ◽  
Borderline Ovarian Tumor ◽  
Early Genes ◽  
Ovarian Tumor Cells

Immune evasion by melanoma and ovarian tumor cells through upregulation of the immunosuppressive molecule CD200

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 2545-2545
Author(s):  
A. Siva ◽  
H. Xin ◽  
F. Qin ◽  
A. Mickel ◽  
S. Faas ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Tumor Cells ◽  
Cell Lines ◽  
Ovarian Tumor ◽  
Cytokine Production ◽  
Ovarian Cancer Cell ◽  
Ovarian Adenocarcinoma ◽  
Ovarian Cancer Cell Lines ◽  
Th1 Cytokine ◽  
Ovarian Tumor Cells

2545 Background: Immune escape by tumors can occur by multiple mechanisms, each a significant barrier to immunotherapy. Upregulation of the immunosuppressive molecule CD200 on chronic lymphocytic leukemia cells inhibits Th1 cytokine production required for an effective cytotoxic T cell response. CD200 expression on human tumor cells in animal models prevents human lymphocytes from rejecting the tumor; treatment with an antagonistic anti-CD200 antibody restored lymphocyte-mediated tumor growth inhibition. This study evaluated CD200 expression on other cancers, and its effect on immune response. Methods: CD200 levels in ovarian adenocarcinoma and metastatic melanoma samples were evaluated by RT-QPCR and immunohistochemistry. Cell-surface CD200 on melanoma and ovarian cancer cell lines was assessed by flow cytometry. The effect of CD200 on cytokine production in mixed lymphocyte reactions (MLR) was assessed by adding the cells to cultures containing human monocyte-derived dendritic cells and allogeneic T cells. Th1 and Th2 cytokines in culture supernatants were detected by ELISA. Results: RT-QPCR showed CD200 expression levels upregulated in serous ovarian adenocarcinoma compared to normal samples. In malignant melanoma, CD200 expression in jejunum metastases was significantly higher than in normal samples, and 2 of 6 lung metastases showed CD200 upregulation. IHC showed strong, membrane-associated CD200 staining on malignant cells of two melanoma patients. Three ovarian cancer patients showed varying levels of CD200 tumor staining; all showed strong stromal staining. CD200 was highly expressed on the cell surface of SK-MEL-24 and SK-MEL-28 melanoma and OV-CAR-3 ovarian cancer cell lines and moderately expressed on the melanoma cell line SK-MEL-5. Addition of these cell lines to MLRs downregulated the production of Th1 cytokines; addition of CD200-negative cell lines did not. Inclusion of an antagonistic anti-CD200 antibody during the culture restored Th1 cytokine responses. Conclusion: Melanoma and ovarian tumor cells can upregulate CD200, thereby potentially suppressing anti-tumor immune responses. Therapy with an antagonistic anti-CD200 antibody may permit an effective cytotoxic immune response against the tumor cells. [Table: see text]

scholarly journals Generation and regulation of human CD4+ IL-17-producing T cells in ovarian cancer

2008 ◽  
Vol 105 (40) ◽  
pp. 15505-15510 ◽  
Author(s):  
Yoshihiro Miyahara ◽  
Kunle Odunsi ◽  
Wenhao Chen ◽  
Guangyong Peng ◽  
Junko Matsuzaki ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
T Cells ◽  
Tumor Cells ◽  
Ovarian Tumor ◽  
Th17 Cells ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Healthy Donors ◽  
Immune Response To Cancer ◽  
Ovarian Tumor Cells

Despite the important role of Th17 cells in the pathogenesis of many autoimmune diseases, their prevalence and the mechanisms by which they are generated and regulated in cancer remain unclear. Here, we report the presence of a high percentage of CD4+ Th17 cells at sites of ovarian cancer, compared with a low percentage of Th17 cells in peripheral blood mononuclear cells from healthy donors and cancer patients. Analysis of cytokine production profiles revealed that ovarian tumor cells, tumor-derived fibroblasts, and antigen-presenting cells (APCs) secreted several key cytokines including IL-1β, IL-6, TNF-α and TGF-β, which formed a cytokine milieu that regulated and expanded human IL-17-producing T-helper (Th17) cells. We further show that IL-1β was critically required for the differentiation and expansion of human Th17 cells, whereas IL-6 and IL-23 may also play a role in the expansion of memory Th17 cells, even though IL-23 levels are low or undetectable in ovarian cancer. Further experiments demonstrated that coculture of naïve or memory CD4+ T cells with tumor cells, APCs, or both could generate high percentages of Th17 cells. Treatment with anti-IL-1 alone or a combination of anti-IL-1 and anti-IL-6 reduced the ability of tumor cells to expand memory Th17 cells. Thus, we have identified a set of key cytokines secreted by ovarian tumor cells and tumor-associated APCs that favor the generation and expansion of human Th17 cells. These findings should accelerate efforts to define the function of this important subset of CD4+ T cells in the human immune response to cancer.

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