Tumor-associated antigen (TAA)-specific CD8⁺ T cell responses inhibit tumor growth. However, T cell tolerance to TAA prevents such responses from developing during immunization with the native TAA. Immunizations with TAA variant peptides however, induce the expansion of TAA-crossreactive cells, though these responses are not always protective. Given that endogenous TAA expression may increase due to factors such as age or tumor burden, we hypothesized that increased TAA expression may result in poor variant peptide-induced expansion of T cells with functional TAA-recognition. To investigate this hypothesis, we used the GP70 TAA model. Although young BALB/c mice demonstrate T cell tolerance to GP70_423-431 (AH1) relative to gp70- deficient mice, expression of GP70 increases with age and AH1-specific responses are decreased. We found that in aging mice with elevated GP70 expression, AH1 variant peptide immunizations do not expand T cells that respond to AH1 stimulation. Variant peptide-specific T cells in naïve mice with high GP70 expression demonstrated a PD-1⁺ anergic or exhausted phenotype, suggesting AH1 recognition, but also a need for adjunct therapies to rescue their expansion upon immunization. Antitumor responses induced by AH1 variant peptide immunizations and many other cancer vaccines rely on endogenous CD8 ⁺ T cells for tumor antigen specificity. Previous studies have suggested that such responses may rely heavily on interferon gamma (IFNγ) for tumor protection. We determined that tumor protection was significantly diminished in IFNγ-deficient mice. Further experiments using IFNγ-neutralizing antibody supported these findings and a protective role for IFNγ at the time of tumor challenge. Previous studies have demonstrated that IFNγ suppresses the expression of GP70 and other TAA in tumor cell lines. We hypothesized that IFNγ may also suppress the expression of GP70 in normal cells, subsequently reducing GP70-specific tolerance. Although detectable differences in GP70 expression or AH1-specific T cell responses were not found in IFNγ-deficient mice, IFNγ-sufficiency did suppress the chemical induction of GP70 in normal cells and enhance AH1-specific T cell responses. Collectively, these studies provide insight into how cancer immunotherapies using TAA variant peptides may be improved and insight into the role of IFNγ in these responses and tolerance to TAA.