Clonal and functional analysis for the augmentation of tumour-infiltrating lymphocytes by interleukin 4

Br J Cancer. 1996 Oct;74(7):1085-9. doi: 10.1038/bjc.1996.494.

Abstract

In the adoptive immunotherapy for cancer, the amounts of induced effector cells play a major role in improving therapeutic efficacy. We have already demonstrated that interleukin 4 (IL-4) augments proliferation of tumour-infiltrating lymphocytes (TILs) without altering the cytotoxic activity against autologous tumour cells. The present study is designed to investigate how IL-4 augments TILs by using established TIL clones in terms of IL-2/IL-2 receptor system. CD4+, CD8+ and CD4+ CD8+ (double positive) TIL clones were established from cancer patients. At clonal level, IL-4 augmented the proliferation of IL-2-activated TIL clones irrespective of phenotypes. In order to clarify the mechanism of IL-4 at clonal level, the blocking assay by anti-IL-2 receptor alpha and beta chain and binding assay of IL-2 on the cell surface and the measurement of the internalisation of IL-2 in the cell were performed. It was clarified that IL-4 up-regulated the IL-2 receptor and then augmented the action of IL-2 molecule on the cell surface stimulated by IL-4. Furthermore, binding IL-2 internalised rapidly into the cells. Thus, it is suggested that signal transduction is augmented and proliferation of TILs is enhanced by IL-4 via the action of IL-2/IL-2 receptor system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA / biosynthesis
  • Humans
  • Interleukin-2 / metabolism*
  • Interleukin-4 / pharmacology*
  • Lymphocyte Activation*
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Receptors, Interleukin-2 / antagonists & inhibitors
  • Receptors, Interleukin-2 / drug effects
  • Receptors, Interleukin-2 / metabolism
  • Time Factors

Substances

  • Interleukin-2
  • Receptors, Interleukin-2
  • Interleukin-4
  • DNA