To study whether CD28KOCD8+ T cells suppress effector cell anti-tumor activity through direct contact or through secreting soluble mediator(s), we added supernatants from anti-CD3/28-activated CD28WTCD8+ (Sup-CD28WTCD8+) and CD28KOCD8+ (Sup-CD28KOCD8+) T cell cultures to P14 CD8+ Teff separately and examined P14 CD8+ Teff anti-tumor activity (Fig. 1d). This evidence concerns the gene CD8A and neoplasm.