An overview of IL-7 biology and its use in immunotherapy

J Immunotoxicol. 2010 Mar;7(1):1-7. doi: 10.3109/15476910903453296.

Abstract

Interleukin (IL)-7 is required for T-cell development as well as for the survival and homeostasis of mature T-cells. In the thymus, the double negative (DN) CD4(-) CD8(-) thymocyte progenitor transition into double positive CD4+ CD8+ cells requires Notch and IL-7 signaling. Importantly, IL-7 seems to have a dose effect on T-cell development and, at high doses, DN progression is blocked. Naïve T-cells in the thymus, and after their exit to the periphery, are dependent on IL-7 and TCR signaling for survival. Upon antigen exposure, they proliferate and differentiate into memory T-cells. Because IL-7 intervenes at all stages of T-cell development and maintenance, it has been introduced recently into clinical trials as an immunotherapeutic agent for cancer patients (of particular note, those who had undergone T-cell depleting therapy) in an attempt to increase their population sizes of CD4+ and CD8+ cells overall, and specifically of CD8+ (CD45RA+)CCR7+ and/or CD27+), CD4+ (CD45RA+CD31+), and CD4+ central memory T-cells (CD45RA(-)CCR7+). Interestingly, IL-7 in humans induced a preferential expansion of naïve T-cells, resulting in a broader T-cell repertoire than before the treatment; this effect was independent of age. This suggests that IL-7 therapy could enhance immune responses in patients with limited naïve T-cell numbers as in aged patients or after disease-induced or iatrogenic T-cell depletion. This overview highlights the role of IL-7 on T-cells in mice and humans.

MeSH terms

  • Animals
  • Antibodies, Monoclonal
  • Cell Differentiation / drug effects
  • Cell Differentiation / immunology
  • Humans
  • Immunity, Cellular / drug effects
  • Immunity, Cellular / immunology
  • Immunotherapy / methods*
  • Interleukin-7 / administration & dosage*
  • Interleukin-7 / immunology*
  • Interleukin-7 / metabolism
  • Lymphocyte Activation
  • Mice
  • Models, Animal
  • Neoplasms / immunology*
  • Neoplasms / therapy
  • Signal Transduction / drug effects
  • Signal Transduction / immunology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • Thymus Gland / growth & development
  • Thymus Gland / immunology
  • Thymus Gland / metabolism

Substances

  • Antibodies, Monoclonal
  • Interleukin-7