IL-7 promotes CXCR3 ligand-dependent T cell antitumor reactivity in lung cancer.
نویسندگان
چکیده
We are evaluating the immune enhancing activities of cytokines for their optimum utility in augmenting cellular immune responses against lung cancer. In this study, we evaluated the mechanism of antitumor responses following IL-7 administration to mice bearing established Lewis lung cancer. IL-7 decreased tumor burden with concomitant increases in the frequency of CD4 and CD8 T lymphocyte subsets, T cell activation markers CXCR3, CD69, and CD127(low), effector memory T cells, and T cell cytolytic activity against parental tumor cells. Accompanying the antitumor responses were increases in IFN-gamma, CXCL9, CXCL10, and IL-12. Individual neutralization of CD4, CD8 T lymphocytes, or the CXCR3 ligands CXCL9 and CXCL10 reversed the antitumor benefit of IL-7, indicating their importance for optimal responses in vivo. Furthermore, IL-7 decreased the tumor-induced apoptosis of T cells with subsequent decrease of the proapoptotic marker Bim. We assessed the impact of IL-7 treatment on regulatory T cells that negatively impact antitumor immune responses. IL-7 decreased regulatory T Foxp3 as well as cell suppressive activity with a reciprocal increase in SMAD7. These results indicate that IL-7 induces CXCR3 ligand-dependent T cell antitumor reactivity in lung cancer.
منابع مشابه
Arteether Exerts Antitumor Activity and Reduces CD4+CD25+FOXP3+ T-reg Cells in Vivo
Background: Chemo-immunotherapy is one of the new achievements for treatment of cancer, by which the success of anti-cancer therapy can be increased. In vitro studies have been shown that Arteether (ARE) induces apoptosis in tumor cells, but not in normal cells. Objective: To investigate the cytotoxic and immunomodulatory properties of Arteether in-vivo and in-vitro. Methods: In this study, we ...
متن کاملMicroenvironment and Immunology CXCR3 Enhances a T-Cell–Dependent Epidermal Proliferative Response and Promotes Skin Tumorigenesis
The chemokine receptor CXCR3 has been proposed to play a critical role in host antitumor responses. In this study, we defined CXCR3-expressing immune cell infiltration in human skin squamous cell carcinomas and then used CXCR3-deficient mice to assess the contribution of CXCR3 to skin tumorigenesis. Our studies employed two established protocols for chemical skin carcinogenesis [methylcholanthr...
متن کاملCXCR3 enhances a T-cell-dependent epidermal proliferative response and promotes skin tumorigenesis.
The chemokine receptor CXCR3 has been proposed to play a critical role in host antitumor responses. In this study, we defined CXCR3-expressing immune cell infiltration in human skin squamous cell carcinomas and then used CXCR3-deficient mice to assess the contribution of CXCR3 to skin tumorigenesis. Our studies employed two established protocols for chemical skin carcinogenesis [methylcholanthr...
متن کاملT cell-derived IL-10 promotes lung cancer growth by suppressing both T cell and APC function.
We have found previously that human lung cancers potently induce T lymphocyte IL-10 production in vitro. To assess the impact of enhanced T cell-derived IL-10 on antitumor immunity in vivo, we utilized transgenic mice expressing IL-10 under the control of the IL-2 promoter. We have shown previously that Lewis lung carcinoma cells (3LL) have more aggressive growth potential in IL-10 transgenic m...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Journal of immunology
دوره 182 11 شماره
صفحات -
تاریخ انتشار 2009