PTPN6 and neoplasm: Using T cell-specific knockout models, it was found that both SHP1 and SHP2 redundantly constrained the differentiation of naïve T cells, predominately by SHP1; SHP2 loss alone enhanced anti-PD-1 therapy efficacy; however, dual loss of SHP1 and SHP2 leads to impaired tumor control as a result of CD4+ T cell activation-dependent cell death [60].