Relative expression levels of Th1 and Th2 cytokine mRNA are independent prognostic factors in patients with ovarian cancer

Kusuda, T.; Shigemasa, Kazushi; Arihiro, Koji; Fujii, Tsuneo; Nagai, Nobuo; Ohama, Koso

doi:10.3892/or.13.6.1153

Cited by 63 publications

(74 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, we observed that the Th1-Th2 balance was shifted toward antitumor Th1 before treatment in the ovarian cancer patients. We also observed that IL-6 was highly expressed in cancer-adjacent tissues but was significantly decreased in ovarian cancer tissues compared with adjacent tissues, consistent with the mRNA data (Kusuda et al, 2005). Therefore, IL-6 might be secreted by cancer-adjacent tissues and released into the blood.…”

Section: Discussionsupporting

confidence: 78%

“…The immune system is greatly affected by cancer treatment; therefore, their findings do not reflect the Th1-Th2 status before treatment. Kusuda et al (2005) determined the mRNA levels of TNFa, IFNg, and IL-12p40 in Th1 cells, and those of IL-6 and IL-10 in Th2 cells in ovarian cancer tissues by quantitative polymerase chain reaction. They thereby determined the correlations between those mRNA levels and the clinical stage, histological grade, and histological type of ovarian cancer.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effects of the balance between type 1 and type 2 T helper cells on ovarian cancer

Hao

Liu

et al. 2016

Genet. Mol. Res.

View full text Add to dashboard Cite

ABSTRACT. The balance between type 1 and type 2 T helper cells (the Th1-Th2 balance) is closely correlated with cancer, but the correlation in ovarian cancer remains unconfirmed. We investigated the Th1-Th2 balance for the diagnosis, treatment, and prognostic evaluation of ovarian cancer. Fifty healthy subjects and 50 ovarian cancer patients were recruited. The levels of various cytokines were determined in sera and ovarian cancer tissues using a Th1-Th2 human cytokine array. The usefulness of TNFa, IFNg, TNFa/IL-4, and IFNg/IL-4 for ovarian cancer diagnosis was assessed based on receiver operating characteristic (ROC) curves. The relationship between the TNFa/IL-4 level and survival time was investigated based on a survival curve. In the ovarian cancer patients, the levels of Th1 factors (IL-2, IFNg, TNFa, and IL-13) increased significantly in the sera, and IFNg and TNFa increased significantly in the ovarian cancer tissues. The levels of Th2 factors (IL-5 and IL-6) increased in the sera, but the level of IL-6 decreased significantly in the ovarian cancer tissues. Serum TNFa/IL-4 and IFNg/IL-4 levels increased significantly in the peripheral blood of the ovarian cancer patients. ROC curve analysis revealed that TNFa, IFNg, TNFa/IL-4, and IFNg/IL-4 levels are useful for ovarian cancer diagnosis, with area under the curve values of 0.831, 0.753, 0.846, and 0.803, respectively. The TNFa/IL-4 level in the ovarian cancer patients was positively correlated with survival time, and the Th1-Th2 balance shifted toward Th1 in the ovarian cancer patients. The TNFa/IL-4 ratio might be useful for the diagnosis and prognosis of ovarian cancer.

show abstract

Section: Discussionsupporting

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Effects of the balance between type 1 and type 2 T helper cells on ovarian cancer

Hao

Liu

et al. 2016

Genet. Mol. Res.

View full text Add to dashboard Cite

show abstract

“…Specifically, tumors that contain a high ratio of CD8 + T cells to FoxP3 + regulatory T cells are associated with prolonged overall survival (14,18). These findings agree with earlier studies showing a positive correlation between survival and expression of IFN-g, a cytokine released by activated CD8 + T cells (21). Thus, it seems that, in many patients undergoing standard treatments, endogenous T cells are able to overcome immunologic barriers to mediate an antitumor effect.…”

supporting

confidence: 82%

CD8+ T Cells Induce Complete Regression of Advanced Ovarian Cancers by an Interleukin (IL)-2/IL-15–Dependent Mechanism

Yang

Wall²,

Milne³

et al. 2007

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: In vitro studies suggest that ovarian cancer evades immune rejection by fostering an immunosuppressive environment within the peritoneum; however, the functional responses of ovarian cancer^specific T cells have not been directly investigated in vivo. Therefore, we developed a new murine model to enable tracking of tumor-specific CD8 + T-cell responses to advanced ovarian tumors. Experimental Design: The ovarian tumor cell line ID8 was transfected to stably express an epitope-tagged version of HER-2/neu (designated Neu OT-I/OT-II

show abstract

“…Thus, we could validate antitumor response with the combination anti-PD-1/RLI in two different endogenous immunological contexts. This observation could be of importance because in patients with cancer many observations have shown that the polarization of T cells may have an impact on the prognosis, Th1 being associated with a good prognosis in most studies and Th2 being mostly associated with a poor prognosis (34)(35)(36)(37). In our study, we showed that anti-PD-1 treatment is effective; however, only a few complete remissions were induced by this treatment (10%).…”

Section: Discussionmentioning

confidence: 53%

IL-15 Trans-Signaling with the Superagonist RLI Promotes Effector/Memory CD8+ T Cell Responses and Enhances Antitumor Activity of PD-1 Antagonists

Desbois

Coutzac

et al. 2016

The Journal of Immunology

View full text Add to dashboard Cite

Tumors with the help of the surrounding environment facilitate the immune suppression in patients, and immunotherapy can counteract this inhibition. Among immunotherapeutic strategies, the immunostimulatory cytokine IL-15 could represent a serious candidate for the reactivation of antitumor immunity. However, exogenous IL-15 may have a limited impact on patients with cancer due to its dependency on IL-15Rα frequently downregulated in cancer patients. In this work, we studied the antitumor activity of the IL-15 superagonist receptor-linker–IL-15 (RLI), designed to bypass the need of endogenous IL-15Rα. RLI consists of human IL-15 covalently linked to the human IL-15Rα sushi+ domain. In a mouse model of colorectal carcinoma, RLI as a stand-alone treatment could limit tumor outgrowth only when initiated at an early time of tumor development. At a later time, RLI was not effective, coinciding with the strong accumulation of terminally exhausted programmed cell death-1 (PD-1)high T cell Ig mucin-3+ CD8+ T cells, suggesting that RLI was not able to reactivate terminally exhausted CD8+ T cells. Combination with PD-1 blocking Ab showed synergistic activity with RLI, but not with IL-15. RLI could induce a greater accumulation of memory CD8+ T cells and a stronger effector function in comparison with IL-15. Ex vivo stimulation of tumor-infiltrated lymphocytes from 16 patients with renal cell carcinoma demonstrated 56% of a strong tumor-infiltrated lymphocyte reactivation with the combination anti–PD-1/RLI compared with 43 and 6% with RLI or anti–PD-1, respectively. Altogether, this work provides evidence that the sushi–IL-15Rα/IL-15 fusion protein RLI enhances antitumor activity of anti–PD-1 treatment and is a promising approach to stimulate host immunity.

show abstract

Relative expression levels of Th1 and Th2 cytokine mRNA are independent prognostic factors in patients with ovarian cancer

Cited by 63 publications

References 0 publications

Effects of the balance between type 1 and type 2 T helper cells on ovarian cancer

Effects of the balance between type 1 and type 2 T helper cells on ovarian cancer

CD8+ T Cells Induce Complete Regression of Advanced Ovarian Cancers by an Interleukin (IL)-2/IL-15–Dependent Mechanism

IL-15 Trans-Signaling with the Superagonist RLI Promotes Effector/Memory CD8+ T Cell Responses and Enhances Antitumor Activity of PD-1 Antagonists

Contact Info

Product

Resources

About