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.

Abstract

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.

• Authors: Lianhua Bai, Philipp Beckhove, Markus Feuerer, Viktor Umansky, Carmen Choi, Florian Schütz Erich-Franz Solomayer, Ingo J Diel, Volker Schirrmacher
• Journal: International journal of cancer (Int J Cancer) Vol. 103 Issue 1 Pg. 73-83 (Jan 01 2003) ISSN: 0020-7136 [Print] United States
• PMID: 12455056 (Publication Type: Journal Article)
• Copyright: Copyright 2002 Wiley-Liss, Inc.

Chemical References

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

Topics

• Animals
• Antigen Presentation
• Antigens, CD (metabolism)
• Antigens, Neoplasm (immunology)
• Apoptosis
• Bone Marrow Cells (immunology)
• Breast Neoplasms (immunology, 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)