Negative regulation of tumor immunosurveillance and antitumor immune responses. (A) CD4⁺CD25⁺ T regulatory cells, induced by peptide presented by class II MHC molecules in the presence of IL-2, may inhibit induction of effector CD4⁺ or CD8⁺ T cells by a contact-dependent or cytokine-dependent mechanism, possibly involving cell surface and/or secreted TGF-β. (B) CD4⁺ NKT cells may be induced by tumor glycolipid presented by CD1d to secrete IL-13, which stimulates Gr-1⁺CD11b⁺ myeloid cells to produce TGF-β, which inhibits induction of CD8⁺ CTLs mediating tumor immunosurveillance. TGF-β may also inhibit CD4⁺ T cells (not shown). Blockade of either mechanism can improve immunosurveillance and the response to vaccines. Other suppressor or negative regulatory cells have been described in other contexts but not as well studied in the context of cancer.