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- 2020.2
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Acute viral infection or vaccination generates highly functional memory CD8 T cells following the Ag resolution. In contrast, persistent antigenic stimulation in chronic viral infection and cancer leads to a state of T-cell dysfunction termed T-cell exhaustion. We and other have recently identified a novel subset of exhausted CD8 T cells that act as stem cells for maintaining virus-specific CD8 T cells in a mouse model of chronic lymphocytic choriomeningitis virus infection. This stem cell-like CD8 T-cell subset has been also observed in both mouse and human tumor models. Most importantly, in both chronic viral infection and tumor models, the proliferative burst of Ag-specific CD8 T cells driven by PD-1-directed immunotherapy comes exclusively from this stem cell-like CD8 T-cell subset. Therefore, a better understanding of the mechanisms how CD8 T-cell subsets are regulated during chronic viral infection and cancer is required to improve the current immunotherapies that restore the function of exhausted CD8 T cells. In this review, we discuss the differentiation of virusspecific CD8 T cells during chronic viral infection, the characteristics and function of CD8 T-cell subsets, and the therapeutic intervention of PD-1-directed immunotherapy in cancer.
목차
ABSTRACT
INTRODUCTION
DEFINING STEM CELL-LIKE CD8 T CELLS DURING CHRONIC VIRAL INFECTION
LOCALIZATION AND MIGRATION OF CD8 T-CELL SUBSETS DURING CHRONIC VIRAL INFECTION
TRANSCRIPTIONAL PROGRAMMING FOR CD8 T-CELL SUBSETS DURING CHRONIC VIRAL INFECTION
ACTION MECHANISM OF PD-1 BLOCKADE DURING CHRONIC VIRAL INFECTION
PRESENCE OF STEM CELL-LIKE T CELLS IN CANCER AND AUTOIMMUNE DISEASE MODELS HAVING PERSISTENT ANTIGENIC STIMULATION
REMAINING QUESTIONS AND FUTURE DIRECTIONS
REFERENCES
참고문헌 (120)
참고문헌 신청
Hashimoto M / 2018 / CD8 T cell exhaustion in chronic infection and cancer : opportunities for interventions / Annu Rev Med 69:301~318
Sharma P / 2015 / The future of immune checkpoint therapy / Science 348:56~61
McLane LM / 2019 / CD8 T cell exhaustion during chronic viral infection and cancer / Annu Rev Immunol 37:457~495
Zajac AJ / 1998 / Viral immune evasion due to persistence of activated T cells without effector function / J Exp Med 188:2205~2213
Gallimore A / 1998 / Induction and exhaustion of lymphocytic choriomeningitis virus-specific cytotoxic T lymphocytes visualized using soluble tetrameric major histocompatibility complex class I-peptide complexes / J Exp Med 187:1383~1393
Sharma P / 2015 / The future of immune checkpoint therapy / Science 348:56~61
McLane LM / 2019 / CD8 T cell exhaustion during chronic viral infection and cancer / Annu Rev Immunol 37:457~495
Zajac AJ / 1998 / Viral immune evasion due to persistence of activated T cells without effector function / J Exp Med 188:2205~2213
Gallimore A / 1998 / Induction and exhaustion of lymphocytic choriomeningitis virus-specific cytotoxic T lymphocytes visualized using soluble tetrameric major histocompatibility complex class I-peptide complexes / J Exp Med 187:1383~1393
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