Dear Editor,The central memory differentiation critically dictates CAR-T cell persistence,which is closely associated with the therapeutic effectiveness in the clinic.It is well accepted that 4-1BB costimulation is su...Dear Editor,The central memory differentiation critically dictates CAR-T cell persistence,which is closely associated with the therapeutic effectiveness in the clinic.It is well accepted that 4-1BB costimulation is superior over CD28 to promote the central memory differentiation and persistence of CAR-T cells.1 However,it is also noticed that CAR-T cells with either co-stimulations are comparably differentiated and persisted,2 especially under immunosuppressive conditions.Factors contributing to the discrepancy remain unknown.Mounting evidences show that programmed cell death protein 1(PD-1)directly affects memory differentiation of T cells upon PD-L1 engagement,3 in addition to limiting proliferation.It is unclear whether PD-1 is involved in the diminished difference in memory differentiation and persistence between CAR-T cells with different co-stimulations.Herein,we examined the memory differentiation of CAR-T cells when PD-1 is activated or not,and consequently the persistence and anti-tumor effects.展开更多
基金supported by funds from the National Key Research and Development Program of China(Grant Numbers 2018YFC1313400,2016YFC1303501)the National Natural Science Foundation of China(Grant Numbers 81771781,U1804281,81502689)the Key Research and Development Project of Henan Provincial Science and Technology Department(Grant Number 192102310035).
文摘Dear Editor,The central memory differentiation critically dictates CAR-T cell persistence,which is closely associated with the therapeutic effectiveness in the clinic.It is well accepted that 4-1BB costimulation is superior over CD28 to promote the central memory differentiation and persistence of CAR-T cells.1 However,it is also noticed that CAR-T cells with either co-stimulations are comparably differentiated and persisted,2 especially under immunosuppressive conditions.Factors contributing to the discrepancy remain unknown.Mounting evidences show that programmed cell death protein 1(PD-1)directly affects memory differentiation of T cells upon PD-L1 engagement,3 in addition to limiting proliferation.It is unclear whether PD-1 is involved in the diminished difference in memory differentiation and persistence between CAR-T cells with different co-stimulations.Herein,we examined the memory differentiation of CAR-T cells when PD-1 is activated or not,and consequently the persistence and anti-tumor effects.
