Autologous dendritic cells derived from CD34+ progenitors and from monocytes are not functionally equivalent antigen-presenting cells in the induction of Melan-A/Mart-127-35-specific CTLs from peripheral blood lymphocytes of melanoma patients with low frequency of CTL precursors

Roberta Mortarini, Andrea Anichini, Massimo Di Nicola, Salvatore Siena, Marco Bregni, Filiberto Belli, Alessandra Molla, Alessandro M. Gianni, Giorgio Parmiani

Research output: Contribution to journalArticlepeer-review

Abstract

Peptide presentation by autologous dendritic cells (DCs) is a new tool to activate tumor antigen-specific T cells in melanoma patients. However, it is not known whether autologous DCs, differentiated by two of the most efficient protocols (from CD34+ progenitors or from monocytes), are equally effective as professional antigen-presenting cells (APCs) when the patients have a low frequency of peptide-specific precursors. To this end, a limiting dilution assay was applied to evaluate the frequency of antigen-specific CTL precursors (CTLps) in peripheral blood of HLA-A*0201+ melanoma patients. Then, from two melanoma patients showing low frequency of CTLps to melanoma antigen-A/melanoma antigen recognized by T cell (Melan-A/Mart-1)27-35 peptide, autologous DCs were differentiated from granulocyte colony- stimulating factor-mobilized CD34+ progenitors or from monocytes. CD34+- and monocyte-derived DCs were characterized by a similar proportion of CD1a+ cells expressing HLA class II antigens and CD54, CD80, and CD86 molecules. Both types of DC presented Melan-A/Mart-127-35 and tyrosinase369- 377 peptides to melanoma-specific CTL clones and were equally effective as peptide-pulsed APCs in the activation of influenza A matrix58-66- specific CTLs from high-frequency precursors (1294/106 and 1789/106 lymphocytes in the two patients). However, efficient activation of Melan- A/Mart-127-35-specific CTLs from low-frequency precursors (158/106 and 77/106 lymphocytes) of the two patients was markedly dependent on the use of peptide-loaded CD34+-derived DCs. These results suggest that CD34+and monocyte-derived DCs are not functionally equivalent APCs for the activation of low-frequency peptide-specific CTLps.

Original languageEnglish
Pages (from-to)5534-5541
Number of pages8
JournalCancer Research
Volume57
Issue number24
Publication statusPublished - Dec 15 1997

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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