Tumor evasion of the immune system by converting CD4+CD25- T cells into CD4+CD25+ T regulatory cells: role of tumor-derived TGF-beta.

نویسندگان

  • Victoria C Liu
  • Larry Y Wong
  • Thomas Jang
  • Ali H Shah
  • Irwin Park
  • Ximing Yang
  • Qiang Zhang
  • Scott Lonning
  • Beverly A Teicher
  • Chung Lee
چکیده

CD4+CD25+ T regulatory (T(reg)) cells were initially described for their ability to suppress autoimmune diseases in animal models. An emerging interest is the potential role of T(reg) cells in cancer development and progression because they have been shown to suppress antitumor immunity. In this study, CD4+CD25- T cells cultured in conditioned medium (CM) derived from tumor cells, RENCA or TRAMP-C2, possess similar characteristics as those of naturally occurring T(reg) cells, including expression of Foxp3, a crucial transcription factor of T(reg) cells, production of low levels of IL-2, high levels of IL-10 and TGF-beta, and the ability to suppress CD4+CD25- T cell proliferation. Further investigation revealed a critical role of tumor-derived TGF-beta in converting CD4+CD25- T cells into T(reg) cells because a neutralizing Ab against TGF-beta, 1D11, completely abrogated the induction of T(reg) cells. CM from a nontumorigenic cell line, NRP-152, or irradiated tumor cells did not convert CD4+CD25- T cells to T(reg) cells because they produce low levels of TGF-beta in CM. Finally, we observed a reduced tumor burden in animals receiving 1D11. The reduction in tumor burden correlated with a decrease in tumor-derived TGF-beta. Treatment of 1D11 also reduced the conversion of CD4+ T cells into T(reg) cells and subsequent T(reg) cell-mediated suppression of antitumor immunity. In summary, we have demonstrated that tumor cells directly convert CD4+CD25- T cells to T(reg) cells through production of high levels of TGF-beta, suggesting a possible mechanism through which tumor cells evade the immune system.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Induction of T Regulatory Subsets from Naïve CD4+ T Cells after Exposure to Breast Cancer Adipose Derived Stem Cells

Background: Adipose derived stem cells (ASCs) provoke the accumulation and expansion of regulatory T cells, leading to the modulation of immune responses in tumor microenvironment. Objective: To assess the effect of tumoral ASCs on the trend of regulatory T cells differentiation. Methods: Peripheral blood naïve CD4+ T cells were co-cultured with ASCs derived from breast cancer or normal breast ...

متن کامل

Tumor Evasion of the Immune System by Converting CD4 CD25 T Cells into CD4 CD25 T Regulatory Cells: Role of Tumor-Derived TGF-

متن کامل

Numerical status of CD4+CD25+FoxP3+ and CD8+CD28- regulatory T cells in multiple sclerosis

Objective(s): Regulatory T cells, including CD4+CD25+Fox3+ and CD8+CD28- cells play an important role in regulating the balance between immunity and tolerance. Since multiple sclerosis is an inflammatory autoimmune disease, regulatory T cells are considered to be involved in its pathogenesis. In this study, we investigated the circulatory numbers of the two mentioned types of regulatory T cells...

متن کامل

Functional and Developmental Analysis of CD4+CD25+ Regulatory T Cells under the Influence of Streptococcal M Protein in Rheumatic Heart Disease

The purpose of this study was to determine the role of streptococcal M protein in naturally-occurring CD4+CD25+ regulatory T cells (nTregs) function and development in rheumatic heart disease in Iraqi patients. Streptococcus pyogenes was isolated for subsequent M protein extraction. Also, peripheral blood nTregs and CD4+ T cells were isolated by using Magnetic Cell Separation System. Tissue cul...

متن کامل

Sclareol Reduces CD4+ CD25+ FoxP3+ T-reg Cells in a Breast Cancer Model in Vivo

Background: Sclareol is a phytochemical used in people's diet in Southeast Asia. Objective: To investigate the immunotherapeutic effectiveness of Sclareol against breast cancer by direct intraperitoneal injection. Methods: Sclareol was isolated and purified from Salvia sclarea. Effect of Sclareol on cell growth inhibition was evaluated by MTT assay. Intraperitoneally injected Sclareol effects o...

متن کامل

ذخیره در منابع من

ذخیره در منابع من قبلا به منابع من ذحیره شده

{@ msg_add @}


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:
  • Journal of immunology

دوره 178 5  شماره 

صفحات  -

تاریخ انتشار 2007