Interleukin 1 beta synergises with interleukin 2 in the outgrowth of autologous tumour-reactive CD8+ effectors

Br J Cancer. 1994 Oct;70(4):625-30. doi: 10.1038/bjc.1994.361.

Abstract

Using peritoneal fluid or pleural effusion obtained from 20 patients with lung, ovarian or metastatic breast cancer, we separated tumour cells from malignant effusion-associated mononuclear cells (MEMNCs) using discontinuous Ficoll-Hypaque density gradients. CD3+ T lymphocytes represented the main population of MEMNCs. The mean +/- s.d. CD4/CD8 ratio of MEMNC suspensions was 1.18 +/- 0.40. MEMNCs proliferated and expanded in vitro with human interleukin 2 (IL-2) either as CD3+ CD8+ cells or as CD3+ CD4+ cells or as mixed populations of CD8+ and CD4+ cells. Preferential cytolytic activity against autologous tumour cells was demonstrated in IL-2-activated MEMNC cultures with excess CD3+ CD8+ cells. In contrast, effectors derived from IL-2-activated cultures with excess CD3+ CD4+ cells lysed both autologous and allogeneic tumour target cells. The addition on day 0 of interleukin 1 beta (IL-1 beta) to MEMNCs cultured in the presence of IL-2 was effective in promoting the growth of CD3+ CD8+ cells and augmenting the cytotoxicity against autologous tumour. Simultaneously, the production of gamma-interferon (IFN-gamma) was increased in these cultures. This is the first report suggesting that IL-1 beta synergises with IL-2 to induce autologous tumour-specific CD8+ cytotoxic T lymphocytes (CTLs) within the MEMNC population. Selective enrichment in T-cell subsets by IL-1 beta may be useful in cellular adoptive immunotherapy using cells isolated from malignant effusions.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Ascitic Fluid / cytology
  • Breast Neoplasms / immunology
  • Breast Neoplasms / pathology
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism*
  • Cell Division / drug effects
  • Cells, Cultured
  • Drug Synergism
  • Female
  • Humans
  • Interferon-gamma / metabolism
  • Interleukin-1 / pharmacology*
  • Interleukin-2 / pharmacology*
  • Lung Neoplasms / immunology
  • Lung Neoplasms / pathology
  • Middle Aged
  • Ovarian Neoplasms / immunology
  • Ovarian Neoplasms / pathology
  • Pleural Effusion, Malignant / cytology
  • T-Lymphocytes, Cytotoxic / drug effects*
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / metabolism

Substances

  • Interleukin-1
  • Interleukin-2
  • Interferon-gamma