Cognate interactions between memory T cells and tumor antigen-presenting dendritic cells from bone marrow of breast cancer patients: bidirectional cell stimulation, survival and antitumor activity in vivo

Int J Cancer. 2003 Jan 1;103(1):73-83. doi: 10.1002/ijc.10781.


Dendritic cells (DC) and T cells were generated from Ficoll separated bone marrow (BM) mononuclear cells of primary operated breast cancer patients according to new cell culture protocols. BM-DC were capable of functioning as professional antigen-presenting cells (APCs) and of inducing autologous antigen-specific memory T-cell responses to either tetanus toxoid recall antigen or to breast cancer antigens. Treatment with lipopolysaccharide (LPS) resulted in phenotypic and functional maturation of BM-DC. When BM-DC, pulsed with breast cancer-associated tumor antigens, were cocultured with autologous patient-derived BM-T cells to allow for cognate breast cancer antigen recognition and stimulation, apoptosis of T cells-which occurred in noncognate coculture systems-was inhibited. Furthermore, in cocultures allowing for antigen-specific cognate interactions, the expression on BM-DC of CD83, MHC class II, CD40 and CD86 molecules was upregulated and the cytokines IL-12 and IFN-alpha were produced in significantly elevated amounts. Adoptive transfer of breast cancer-reactive memory T cells together with APCs into human breast cancer-bearing NOD/SCID mice caused a regression of the tumor and prolonged survival of the animals. This was not the case when such animals had been treated by transfer of reactivated BM T cells without BM-DCs. Our findings suggest that cognate interactions between cancer patient-derived memory BM-T cells and tumor antigen-presenting BM-DCs are important for reciprocal cell stimulation, survival and therapeutic activity.

MeSH terms

  • Animals
  • Antigen Presentation
  • Antigens, CD / metabolism
  • Antigens, Neoplasm / immunology*
  • Apoptosis
  • Bone Marrow Cells / immunology*
  • Breast Neoplasms / immunology*
  • Breast Neoplasms / pathology
  • Cell Communication
  • Cell Survival
  • Cytokines / metabolism
  • Dendritic Cells / immunology*
  • Female
  • Histocompatibility Antigens Class II / metabolism
  • Humans
  • Immunologic Memory
  • Immunotherapy, Adoptive
  • In Vitro Techniques
  • Interferon-gamma / biosynthesis
  • Lymphocyte Activation
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • T-Lymphocytes / immunology*


  • Antigens, CD
  • Antigens, Neoplasm
  • Cytokines
  • Histocompatibility Antigens Class II
  • Interferon-gamma