Given our previous findings of functional deficiency in the Type-1 TAA-specific CD4+ T cell responses in melanoma and RCC patients (17, 18) and reports for the preferential sensitivity of Th1-type CD4+ T cells to AICD under conditions of chronic antigen-stimulation (27, 28), we next investigated whether HLA-DR4/TAA peptide tetramer+ CD4+ T cells in patients were prone to express an Annexin-V+ pro-apoptotic phenotype, and whether such phenotypes diverged from those associated with HLA-DR4/FluM1-tetramer+ CD4+ T cells (Figure 4A). The gene discussed is ANXA5; the disease is renal cell carcinoma.