Additionally, De Gruijl et al. have demonstrated that prolonged overall survival following treatment with a cancer vaccine (GVAX) in combination with ipilimumab was observed in patients with advanced prostate cancer who had high pretreatment frequencies of CD4+ CTLA-4+, CD4+ PD-1+, or differentiated (non-naïve) CD8+ T cells, or alternatively low pre-treatment frequencies of regulatory T cells or differentiated CD4+ T cells [31]. Here, CD4 is linked to cancer.