Specifically, BE-induced gain-of-function (GOF) mutations in PIK3CD and PIK3R1 in T cells, including those engineered with a melanoma-specific T cell receptor or in various generations of CD19 CAR-Ts, lead to enhanced signaling, cytokine production, and the ability to effectively kill melanoma and leukemia cells 120. Here, PIK3R1 is linked to melanoma.