Activating CD28 mutations recur in 10-11% of AITL (97, 98), and in-frame fusions involving CD28, CTLA4 and ICOS recur in 7% of ATL along with CD28 focal gains and missense mutations, all of which result in continuous or prolonged co-stimulatory signaling (38). This evidence concerns the gene ICOS and angioimmunoblastic T-cell lymphoma.