Initial studies described the ability of CD4+CD25+ T regulatory (Treg) cells in suppressing autoimmune diseases in animal models. An emerging interest has focused on the potential role of Treg cells in cancer development and progression as they have been shown to suppress anti-tumor immunity. In the present study, CD4+CD25- T cells cultured in conditioned medium (CM) derived from tumor cells RENCA or TRAMP-C2, possess characteristics as those of naturally occurring Treg cells. Further investigation revealed a critical role of tumor-derived TGF-beta in converting CD4+CD25- T cells into Treg cells, as a neutralizing antibody against TGF-beta, 1D11, completely abrogated this conversion. CM from a non-tumorigenic cell line, NRP-152, or irradiated tumor cells did not induce Treg cell conversion because they produced low levels of TGF-beta. We also observed a reduced tumor burden in animals receiving 1D11. This reduction was associated with a decrease in Treg cell conversion. In summary, we demonstrated that tumor cells can directly convert CD4+CD25- T cells to Treg cells through production of high levels of TGF-beta, suggesting a possible mechanism through which tumors evade the immune system. Initial studies described the ability of CD4+CD25+ T regulatory (Treg) cells in suppressing autoimmune diseases in animal models. An emerging interest has focused on the potential role of Treg cells in cancer development and progression as they have been shown to suppress anti-tumor immunity. In the present study, CD4+CD25- T cells cultured in conditioned medium (CM) derived from tumor cells RENCA or TRAMP-C2, possess characteristics as those of naturally occurring Treg cells. Further investigation revealed a critical role of tumor-derived TGF-beta in converting CD4+CD25- T cells into Treg cells, as a neutralizing antibody against TGF-beta, 1D11, completely abrogated this conversion. CM from a non-tumorigenic cell line, NRP-152, or irradiated tumor cells did not induce Treg cell conversion because they produced low levels of TGF-beta. We also observed a reduced tumor burden in animals receiving 1D11. This reduction was associated with a decrease in Treg cell conversion. In summary, we demonstrated that tumor cells can directly convert CD4+CD25- T cells to Treg cells through production of high levels of TGF-beta, suggesting a possible mechanism through which tumors evade the immune system.

Last modified

• 06/26/2018

Creator

• Victoria Chunyan Liu

DOI

• https://doi.org/10.21985/N2B400

Subject

• Integrated Graduate Program in the Life Sciences

Keyword

• Biology

Date created

• 2007-05-15

Resource type

• Dissertation

Rights statement

• In Copyright