Memory T cell, exhaustion, and tumor immunity

Makoto Ando, Minako Ito, Tanakorn Srirat, Taisuke Kondo, Akihiko Yoshimura

研究成果: Review article

抄録

CD8+T cells are important in protective immunity against intracellular pathogens and tumors. In chronic infections or cancer, CD8+T cells are constantly exposed to antigens and inflammatory signals. Such excessive and constitutive signals lead to the deterioration of T cell function, called ‘exhaustion’. Exhausted T cells are characterized by low proliferation in response to antigen stimulation, progressive loss of effector function (cytokine production and killing function), expression of multiple inhibitory receptors such as PD-1, Tim3, and LAG3, and metabolic alterations from oxidative phosphorylation to glycolysis. These dysfunctions are associated with altered transcriptional programs and epigenetic regulations and recent studies suggested that NR4a and TOX transcription factors are deeply involved in exhaustion phenotypes. However, an increase the early memory T cells including stem cell memory T (TSCM) cells is critical for T cell persistence and efficient tumor killing especially for adoptive cancer immunotherapy such as CAR-T cell therapy. An increasing amount of evidence supports the therapeutic potential of targeting exhausted T cells and TSCM cells. We have begun to understand the molecular mechanisms of T cell exhaustion and early memory formation, and the clinical application of converting exhausted T cells to rejuvenated early memory T cells is the goal of our study.

元の言語English
ジャーナルImmunological Medicine
DOI
出版物ステータスAccepted/In press - 2019 1 1

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Immunity
T-Lymphocytes
Neoplasms
Adoptive Immunotherapy
Antigens
Oxidative Phosphorylation
Glycolysis
Cell- and Tissue-Based Therapy
Epigenomics
Transcription Factors
Stem Cells
Cytokines
Phenotype
Infection

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

これを引用

Memory T cell, exhaustion, and tumor immunity. / Ando, Makoto; Ito, Minako; Srirat, Tanakorn; Kondo, Taisuke; Yoshimura, Akihiko.

:: Immunological Medicine, 01.01.2019.

研究成果: Review article

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