CTLA4 and carcinoma: In preclinical models it is well established that NKG2D ligand over-expression on tumor cells results in an increased priming and activation of tumor-specific CD8+ T cells and long lasting T-cell memory responses even against NKG2D-negative tumor cells47: (i) Induction of NKG2D ligands on carcinoma cells boosts anti-tumor effects of CTLA-4 blockade48, and (ii) treatment with immune stimulating cytokines such as IL-2 and IL-12 is more effective against NKG2D ligand expressing tumors49.