Epigenetic regulation of T cell exhaustion Julia A. Belk Bence Daniel Ansuman T. Satpathy Nature Immunology(2022) ‘Stem-like’ precursors are the fount to sustain persistent CD8+ T cell responses Dietmar Zehn Robert Thimme Annette Oxenius ...
CD8T cells are critical mediators of antitumor immunity but differentiate into a dysfunctional state, known as T cell exhaustion, after persistent T cell receptor stimulation in the tumor microenvironment (TME). Exhausted T (T) cells are characterized by upregulation of coinhibitory molecules and ...
Loss of Ptpn2 enhances Tim-3+CD8+ T cell differentiation in tumors. Given the importance of dysfunctional T cell subpopulations in tumors4,18,22–27, we next asked whether Ptpn2 also regulates the balance and functions of CD8+ T subpopulations in responses to tumors. We cotransferred congenic...
Conditional gene deletion showed a cell-intrinsic requirement of CD28 for CD8 T cell proliferation after PD-1 blockade. B7-costimulation was also necessary for effective PD-1 therapy in tumor-bearing mice. In addition, we found that CD8 T cells proliferating in blood after PD-1 therapy of ...
Functional impairment of antigen-specific T cells is a defining characteristic of many chronic infections, but the underlying mechanisms of T-cell dysfunction are not well understood. To address this question, we analysed genes expressed in functionally impaired virus-specific CD8 T cells present in ...
CD8 T cell exhaustionimmunotherapyTCF-1 is a key transcription factor in progenitor exhausted CD8 Tcells (Tex). Moreover, this Tex cell subset mediates responses to PD-1 checkpoint pathway blockade. However, the role of the transcription factor TCF-1 in early fate decisions and initial ...
Sex differences in renal cell carcinoma: a single-cell analysis reveals exhausted CD8+ T-cells highly infiltrated in males Kang Ning, Yulu Peng, Yue Jiang, Zhen Li, Xin Luo, Lede Lin, Minhua Deng, Yi Wu, Tingxuan Huang, Yixin Huang, Ye Xie, Xiaofeng Yang, Manhuai Zha...
CD39 expressed by CD8+T cells in chronic infection is enzymatically active, co-expressed with PD-1, marks cells with a transcriptional signature of T cell exhaustion and correlates with viral load in HIV and HCV. In the mouse model of chronic Lymphocytic Choriomeningitis Virus infection, virus-...
In the mouse model of chronic Lymphocytic Choriomeningitis Virus infection, virus-specific CD8+ T cells contain a population of CD39high CD8+ T cells that is absent in functional memory cells elicited by acute infection. This CD39high CD8+ T cell population is enriched for cells with the ...
Programmed death-1 (PD-1) regulates T cell exhaustion during chronic infections. Blocking the PD-1:PD-ligand (PD-L) pathway reinvigorates exhausted CD8 T cells. Exactly how blocking PD-1:PD-L interactions improves T cell immunity, however, remains unclear. PD-1:PD-L blockade could reprogram...