CTLA-4 and CD28 are co-stimulatory receptors on T-cells. Because of their structural similarity, they compete for the same ligands (CD80 and CD86), which are located on the surface of antigen-presenting cells. A binding of CD28 activates T-cells, in contrast to that CTLA-4 acts as a negative regulator of T-cell function. The activity of CTLA-4 is influenced by genetic variants (polymorphisms, SNPs), which lead to an increased or decreased number of the CTLA-4 receptors on T cells and thus indirectly interfere with the immune response. A decreased number of CTLA-4 receptors may lead to autoimmune diseases and an increased number to cancer. The blockade of CTLA-4 by ipilimumab (= monoclonal antibodies) can cause an increased immune response against tumour cells but also immune related adverse events. Polymorphisms in the CTLA-4 gene may influence the effectiveness of ipilimumab.