CTLA4 and Autoimmunity: This variant has been associated with an increased susceptibility to systemic sclerosis,38 and its involvement in our signature is consistent with the known increased risk of irAEs in patients with known pre-existing autoimmunity.39 It is also pertinent to note that others have found that the level of the IL-10 cytokine predicts response to anti-CTLA-4 therapy, supporting the importance of this signaling pathway in immune response.34