In:
International Journal of Cancer, Wiley, Vol. 103, No. 1 ( 2003-01), p. 73-83
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‐α 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. © 2002 Wiley‐Liss, Inc.
Type of Medium:
Online Resource
ISSN:
0020-7136
,
1097-0215
Language:
English
Publisher:
Wiley
Publication Date:
2003
detail.hit.zdb_id:
218257-9
detail.hit.zdb_id:
1474822-8
