Tumor infiltrating lymphocytes from acute myeloid leukemia marrow can be reverted to CD45RA+ central memory state by reactivation in SIP (Simulated Infective Protocol)

Abstract

Simulated Infective Protocol (SIP) is an ex-vivo culture system modeled after the temporal changes of essential cytokines in an acute infection, and previously proven successful in converting T lymphocytes harvested and activated from peripheral blood of normal donors, to revertant CD45RA + Central Memory T lymphocytes (Tcmra) demonstrating properties akin to T Memory Stem Cells (Tscm). In this study, we applied similar SIP on tumor infiltrating lymphocytes (TIL) from bone marrow of patients diagnosed with acute myeloid leukemia (AML), and replicated the feasibility to convert activated TILs into Tcmra phenotype. These revertant Tcmra lymphocytes re-expressed CD45RA+, CCR7+, CD62L + and CD127+, shown improved survivability with longer telomere length, expressed memory properties including higher Eomes to Tbet ratio, and exhibited cytotoxicity against autologous AML blast cells.