The anti-CTLA4 therapies are associated with more severe and systemic autoimmune adverse events such as colitis and hypophysitis; the anti-PD1 therapies are associated with less severe and somewhat peripheral reactions such as pneumonitis and thyroiditis.148 Second, given the fact that these agents act on different steps of the immune cascade, they might have a positive but also negative synergetic effect when combined.147. The gene discussed is CTLA4; the disease is colitis.