If this is the landscape in the periphery, in the tumor site PD1+CD28+ T cells exhibited both frequency enrichment and functional fitness, as recently highlighted likely due to higher cis-B7/CD28 interaction [48], also reminding the ability of myeloid APC niches to generate polyfunctional effector CD8+ T cells, specifically associated with CD28 co-stimulation in response to PD1 blockade [21]. The gene discussed is CD8A; the disease is neoplasm.