Regulatory CD4(+)CD25(+) T cells in tumors from patients with early-stage non-small cell lung cancer and late-stage ovarian cancer

Immunosuppression may contribute to the progression of cancer, In this stud y we assessed the structural and functional status of T tells from tumor sp ecimens obtained from patients with early stage non-small cell lung cancer and Late-stage ovarian cancer, Although some groups have described structur al alterations in the TCR in patients with other malignancies, we did not o bserve decreased expression of the CD3 zeta subunit in the tumor-associated T cells. However, increased percentages of CD4(+)CD25(+) T cells were obse rved in the non-small cell lung cancer tumor-infiltrating lymphocytes and o varian cancer tumor-associated lymphocytes, Furthermore, these CD4+CD25+ T cells were found to secrete transforming growth factor-beta, consistent wit h the phenotype of regulatory T cells. Despite a generalized expression of lymphocyte activation markers in the tumor-associated T-cell populations, t he CD8(+) T cells expressed low levels of CD25, To determine whether expres sion of CD25 could be restored on the CDS cells, tumor-associated T cells w ere stimulated with anti-CD3 and anti-CD28 monoclonal antibodies. After sti mulation, nearly all of the CD8 T cells expressed CD25, Furthermore, despit e the low levels of interleukin 2, IFN-gamma, and tumor necrosis factor-cu secretion by the tumor-associated and peripheral blood T cells at baseline, stimulation with anti-CD3 and anti-CD28 monoclonal antibodies significantl y increased the fraction of cells producing these cytokines, Thus, tumor-as sociated T cells from patients with early and late-stage epithelial tumors contain increased proportions of CD4+CD25+ T cells that secrete the immunos uppressive cytokine transforming growth factor-beta, Furthermore, our resul ts are consistent with previous reports showing impaired expression of CD25 on CD8(+) T cells in cancer patients. Finally, increased lymphocyte costim ulation provided by triggering the CD28 receptor is able to increase CD25 e xpression and cytokine secretion in tumor-associated T cells. These observa tions provide evidence for the contribution of regulatory T cells to immune dysfunction in cancer patients.