Tumour-induced polarization of tumour vaccine-draining lymph node T cells to a type 1 cytokine profile predicts inherent strong immunogenicity of the tumour and correlates with therapeutic efficacy in adoptive transfer studies

Immunology. 2003 Mar;108(3):409-19. doi: 10.1046/j.1365-2567.2003.01596.x.

Abstract

Previously we have shown that vaccination with the poorly immunogenic B16BL6-D5 melanoma (D5) elicits a dominant type 2 (T2) cytokine response that fails to protect the host from a subsequent tumour challenge. Here we investigated whether the inherent immunogenicity of a tumour can be correlated with its ability to bias the anti-tumour cytokine response towards either a type 1 (T1) or a T2 profile. The immune response to six tumours of different inherent immunogenicity was assayed. By isolating l-selectinlow T cells from tumour vaccine draining lymph nodes (TVDLN), it was possible to detect tumour-specific cytokine responses from both immunogenic, poorly immunogenic and non-immunogenic tumours. Immunogenic tumours (MCA-304, MCA-309, MPR-4) induced a predominant tumour-specific T1 cytokine response. In contrast, weakly (MCA-310, MPR-3) and poorly/non-immunogenic tumours (MPR-5, D5) sensitized T cells with a predominant tumour-specific T2 cytokine response. A significant correlation (P < 0.025) between immunogenicity and the ratio of tumour-specific interferon-gamma : interleukin-4 (IL-4) secretion by TVDLN T cells was identified. We then documented that non-therapeutic T cells primed by the poorly immunogenic D5, recognized "tumour-rejection" antigens and that reprogramming their cytokine response, by in vitro culture with IL-12 and anti-IL-4, to a T1 profile uncovered therapeutic efficacy. In contrast, TVDLN T cells primed by a therapeutic vaccine lose therapeutic efficacy when cultured with IL-4. These results provide insights into the development of a protective anti-tumour immune response and strengthen the hypothesis that a T1 cytokine response is critical for T-cell-mediated tumour regression.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cancer Vaccines / immunology*
  • Cytokines / biosynthesis*
  • Female
  • Immune Tolerance
  • Immunotherapy, Adoptive*
  • Interleukin-4 / immunology
  • Lymph Nodes / immunology
  • Melanoma, Experimental / immunology
  • Melanoma, Experimental / prevention & control
  • Mice
  • Mice, Inbred C57BL
  • Neoplasms, Experimental / immunology*
  • Neoplasms, Experimental / prevention & control
  • Th1 Cells / immunology*
  • Th2 Cells / immunology
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Cancer Vaccines
  • Cytokines
  • Tumor Necrosis Factor-alpha
  • Interleukin-4