Regulation of T-cell immune exhaustion and cancer immunotherapy

Shingo Eikawa, Heiichiro Udono

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

In chronic infectious diseases and cancer, CD8+ T cells specific for viral and/or tumor antigens undergo repeated T cell receptor (TCR) stimulation due to the persistence of pathogens or cancer cells, gradually losing their ability to secrete interleukin 2 (IL-2), tumor necrosis factor-α (TNF-α), and interferon-γ-(IFN-γ). These CD8+ T cells are finally eliminated by apoptosis, a process referred to as immune exhaustion. The worsening immune function is accompanied by phenotypic changes in CD8+ T cells, for example, by changes in the expression of exhaustion markers such as programmed cell death protein 1 (PD-1), cytotoxic T-lymphocyte antigen 4 (CTLA-4), T cell immunoglobulin mucin 3 (TIM-3), and lymphocyte activation gene 3 (LAG-3). The exhaustion molecules on CD8+ T cells interact with their respective ligands and induce negative signals in activated T cells, leading to CD8+ T cell dysfunction. In 2013, the combined use of anti-PD-1 and anti-CTLA-4 antibodies was shown to induce extraordinary anti-tumor effects in patients with advanced melanoma. The regulation of exhausted CD8+ T cells has now emerged as a promising therapy to treat cancer.

Original languageEnglish
Pages (from-to)1066-1070
Number of pages5
JournalGan to kagaku ryoho. Cancer & chemotherapy
Volume41
Issue number9
Publication statusPublished - Sep 1 2014

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Immunotherapy
T-Lymphocytes
Neoplasms
CTLA-4 Antigen
Programmed Cell Death 1 Receptor
Mucin-3
Viral Tumor Antigens
Lymphocyte Activation
T-Cell Antigen Receptor
Interferons
Interleukin-2
Communicable Diseases
Immunoglobulins
Melanoma
Chronic Disease
Tumor Necrosis Factor-alpha
Apoptosis
Ligands
Antibodies
Genes

Keywords

  • Cd8 T cell
  • Immune exhaustion

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Regulation of T-cell immune exhaustion and cancer immunotherapy. / Eikawa, Shingo; Udono, Heiichiro.

In: Gan to kagaku ryoho. Cancer & chemotherapy, Vol. 41, No. 9, 01.09.2014, p. 1066-1070.

Research output: Contribution to journalArticle

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