Since such deficiency was acutely evident in patients with active disease (AD), where chronic stimulation of anti-tumor CD4+ T cells would be expected and activation-induced cell death may be prevalent, we employed MHC Class II-peptide tetramers to characterize the frequency and apoptotic status of TAA- vs. influenza (FluM1) virus-specific CD4+ T cells in the peripheral blood of HLA-DR*0401+ patients with melanoma or renal cell carcinoma. Here, CD4 is linked to hereditary clear cell renal cell carcinoma.