Among over 100 members of the PTP family, protein-tyrosine phosphatase 1B (PTP-1B) and T-cell protein-tyrosine phosphatase (PTPN2, TCPTP) have the most closely related homology (72%), sharing identical catalytic subunits. Significantly, together they serve nonredundant functions suppressing CD8+ T-cell activation and negatively impacting on tumor cells antigen presentation. Agents that can simultaneously target both PTP-1B and TCPTP have the potential to provide therapeutic benefits in the context of cancer and/or diabetes by increasing T-cell activation and reversing suppression of tumor cell MHC1 expression.