Other significantly up-regulated genes in “T cell high” tumors included many immune checkpoint molecules, including both co-stimulatory molecules (ICOS (p=0.0001) and CD28 (p=0.0002), as well as co-inhibitory molecules associated with an exhausted phenotype in human cancer patients (PD-1 (p=0.0001), CTLA-4 (p=0.0014) [reviewed in Chen, et al. This evidence concerns the gene CD28 and cancer.