In vitro dendritic cell generation and lymphocyte subsets in myeloma patients: influence of thalidomide and high-dose chemotherapy treatment.
While vaccination with antigen-pulsed dendritic cells (DCs) represents a promising therapeutic strategy in multiple myeloma (MM), clinical benefit, so far, has been limited to individual patients. To identify potential problems with this approach, we have analyzed the influence of treatment parameters, in particular high-dose chemotherapy (HD-CTX) and thalidomide, on in vitro DC generation and peripheral blood lymphocyte subsets in MM patients. From a total of 25 MM patients, including 14 patients on thalidomide treatment and 11 after HD-CTX, in vitro DC generation from peripheral blood monocytes under serum-free condition was investigated. In addition, peripheral blood lymphocyte subsets were assessed in 17 patients including 10 patients on thalidomide treatment and 9 patients after HD-CTX. Efficient in vitro generation of DCs (median 7.1x10(6)/100 ml peripheral blood; range 0.1-42.5x10(6)/100 ml peripheral blood) expressing DC-typical surface markers was observed in 23 MM patients (92%), although reduced expression of CD1a, CD40, CD83, and HLA-DR was observed in patients treated with thalidomide. With respect to lymphocyte subsets, MM patients showed significantly (p<0.05) reduced B and CD4+ lymphocytes in the peripheral blood. This effect was most prominent within 6 months of HD-CTX and in patients receiving thalidomide (usually in combination with CTX). CD8+ lymphocytes were significantly increased in MM patients. Thus, despite the well-known deficiencies in their immune system, adequate numbers of DCs can be generated in most myeloma patients. In patients treated with thalidomide, however, it remains to be seen whether the reduced expression of co-stimulatory molecules has functional relevance.
Schütt
Philipp
P
Department of Internal Medicine (Cancer Research), West German Cancer Center, University of Duisburg-Essen Medical School, Hufelandstrasse 55, 45122 Essen, Germany. philipp.schuett@uni-essen.de
Buttkereit
Ulrike
U
Brandhorst
Dieter
D
Lindemann
Monika
M
Schmiedl
Sven
S
Grosse-Wilde
Hans
H
Seeber
Siegfried
S
Nowrousian
Mohammad Resa
MR
Opalka
Bertram
B
Moritz
Thomas
T
D000954:Antigens, Surface / Q000032:analysis; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015847:Interleukin-4 / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013792:Thalidomide / Q000627:therapeutic use*
D000954:Antigens, Surface; D007166:Immunosuppressive Agents; D015847:Interleukin-4; D013792:Thalidomide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor