The composition of tumor infiltrating lymphocytes (TIL) is heterogeneous. In addition, the ratio of various subpopulations in the tumor microenvironment is highly dependent on the nature of the host's immune response. Here, we characterize Foxp3-expressing CD8(+) T cells in the
tumor that demonstrate effector function and accumulate in the context of an effective anti-
tumor response. CD8(+) Foxp3(+) T cells are induced in TIL in regressing
tumors of FVB/N mice treated with a
GM-CSF secreting HER-2/neu targeted whole cell
vaccine. Foxp3 expression in
tumor antigen-specific CD8 T cells is restricted to the tumor microenvironment and influenced by cues in the
tumor. Interestingly, Foxp3(+) and Foxp3(-) CD8(+) T cells have similar IFN-γ production and
antigen-specific degranulation after stimulation with RNEU(420-429) , the immunodominant HER-2/neu (neu)
epitope in this model. Adoptive transfer studies, using RNEU((420-429)) -specific effector T cells into neu-N mice (a model that results in immune tolerance to neu), confirm that CD8(+) Foxp3(+) T cells are present in
tumors only if there is an existing pool of
tumor-rejecting effector T cells. CD8(+) Foxp3(+) TILs mark the presence of
tumor-rejecting
antigen-specific T cells and their accumulation serves as a marker for an effective T cell response.