T cells are central components of the adaptive immune system and play key roles in antitumor and antiviral responses.The diverse cell fates of T cells enable them to respond to different durations and strengths of ant...T cells are central components of the adaptive immune system and play key roles in antitumor and antiviral responses.The diverse cell fates of T cells enable them to respond to different durations and strengths of antigen stimulation and various cytokine milieus in a context-dependent manner.During acute infection or vaccination,T cells differentiate into effector cells and later develop into memory cells after antigen clearance,which mediate immune protection against the same antigen.In contrast,during cancer and chronic infection,T cells fail to enter the canonical effector or memory cell differentiation path.Instead,antigen-specific T cells enter a dysfunctional,partially responsive state called exhaustion.Exhausted T cells are heterogeneous.A subset of exhausted T cells exhibits stem cell-like properties.These stem-like T cells sustain immunity through self-renewal and repopulation of terminally differentiated progenies.Stem-like properties are critical for T cell immunity induced by immunotherapy.This review summarizes recent advances in understanding the molecular mechanisms controlling the exhaustion and stemness of T cells and explores the potential of rewiring these circuits to increase the efficiency of T-cell-based immunotherapy.展开更多
文摘T cells are central components of the adaptive immune system and play key roles in antitumor and antiviral responses.The diverse cell fates of T cells enable them to respond to different durations and strengths of antigen stimulation and various cytokine milieus in a context-dependent manner.During acute infection or vaccination,T cells differentiate into effector cells and later develop into memory cells after antigen clearance,which mediate immune protection against the same antigen.In contrast,during cancer and chronic infection,T cells fail to enter the canonical effector or memory cell differentiation path.Instead,antigen-specific T cells enter a dysfunctional,partially responsive state called exhaustion.Exhausted T cells are heterogeneous.A subset of exhausted T cells exhibits stem cell-like properties.These stem-like T cells sustain immunity through self-renewal and repopulation of terminally differentiated progenies.Stem-like properties are critical for T cell immunity induced by immunotherapy.This review summarizes recent advances in understanding the molecular mechanisms controlling the exhaustion and stemness of T cells and explores the potential of rewiring these circuits to increase the efficiency of T-cell-based immunotherapy.
