Exhausted T (Tex) cells are a distinct state of T cell differentiation that arise during chronic infections and cancer. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, metabolic dysregulation, poor memory recall, and poor homeostatic self-renewal. Tex are considered by many as a distinct lineage of T cells due to their distinct transcriptional and epigenetic programs. Tex reflect failure of the immune response to eradicate cancer and chronic viral infection. Thus, following their characterization Tex represented a prime target for therapeutic interventions in the past decade, since reversing this dysfunctional state hold promise for controlling cancer and chronic viral infections.
The ability to reinvigorate Tex cells through immunotherapeutic strategies revolutionized cancer treatment. Checkpoint blockade that relies on blocking inhibitory receptors, such as PD-1, has shown great success clinically in cancer treatment settings, and highlighted the therapeutic potential of targeting Tex. However, not all patients benefit from the currently available immunotherapies, highlighting the importance of deciphering the mechanisms underlying the development of T-cell exhaustion, as well as the potential mechanisms of recovery and reversal of the exhaustion state. Deeper insights into the biology of Tex, as well as mechanisms and developmental pathways of exhaustion, and recovery/reversal of exhaustion are pivotal for enhancing immunotherapies for cancer and chronic infections. Additionally, Tex -similar to other immune cell types- are heterogeneous, and Tex populations include stem-like progenitor subset(s), intermediate subsets, and more terminally differentiated subsets with unique characteristics and differential responses to immunotherapy. Better understanding of the subset-dynamics would aid the informed design of targeted intervention strategies.
Under this Research Topic, we welcome the Original Research Articles, Methods, and Reviews that explore cellular, transcriptional and epigenetic mechanisms of Tex development, as well as the underlying mechanisms of recovery/reversal from T-cell exhaustion in various models and clinical settings.
The following direction are especially welcome:
(1) Identification of previously underappreciated pathways of specific interest in the development of T-cell exhaustion.
(2) Mapping transcriptional and/or epigenetic networks involved in recovery/reversal from T-cell exhaustion.
(3) The potential action of specific interventions that reverse the dysfunctional state associated with Tex, and have the potential of reversing T-cell exhaustion.
Exhausted T (Tex) cells are a distinct state of T cell differentiation that arise during chronic infections and cancer. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, metabolic dysregulation, poor memory recall, and poor homeostatic self-renewal. Tex are considered by many as a distinct lineage of T cells due to their distinct transcriptional and epigenetic programs. Tex reflect failure of the immune response to eradicate cancer and chronic viral infection. Thus, following their characterization Tex represented a prime target for therapeutic interventions in the past decade, since reversing this dysfunctional state hold promise for controlling cancer and chronic viral infections.
The ability to reinvigorate Tex cells through immunotherapeutic strategies revolutionized cancer treatment. Checkpoint blockade that relies on blocking inhibitory receptors, such as PD-1, has shown great success clinically in cancer treatment settings, and highlighted the therapeutic potential of targeting Tex. However, not all patients benefit from the currently available immunotherapies, highlighting the importance of deciphering the mechanisms underlying the development of T-cell exhaustion, as well as the potential mechanisms of recovery and reversal of the exhaustion state. Deeper insights into the biology of Tex, as well as mechanisms and developmental pathways of exhaustion, and recovery/reversal of exhaustion are pivotal for enhancing immunotherapies for cancer and chronic infections. Additionally, Tex -similar to other immune cell types- are heterogeneous, and Tex populations include stem-like progenitor subset(s), intermediate subsets, and more terminally differentiated subsets with unique characteristics and differential responses to immunotherapy. Better understanding of the subset-dynamics would aid the informed design of targeted intervention strategies.
Under this Research Topic, we welcome the Original Research Articles, Methods, and Reviews that explore cellular, transcriptional and epigenetic mechanisms of Tex development, as well as the underlying mechanisms of recovery/reversal from T-cell exhaustion in various models and clinical settings.
The following direction are especially welcome:
(1) Identification of previously underappreciated pathways of specific interest in the development of T-cell exhaustion.
(2) Mapping transcriptional and/or epigenetic networks involved in recovery/reversal from T-cell exhaustion.
(3) The potential action of specific interventions that reverse the dysfunctional state associated with Tex, and have the potential of reversing T-cell exhaustion.
