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Blood, Vol. 92 No. 9 (November 1), 1998:
pp. 3381-3387
Resistance to Cytotoxic Chemotherapy Induced by CD40 Ligand in
Lymphoma Cells
Nathalie Voorzanger-Rousselot,
M.-C. Favrot, and
Jean-Yves Blay
From Unité Cytokine et Cancer, Unité INSERM U453, Centre
Léon Bérard, Lyon, France.
The modulation of the cytotoxic effects of an anthracyclin by CD40L
was investigated in five non-Hodgkin's lymphoma (NHL) cell lines
(Daudi, Raji, BJAB, BL36, BL70). Incubation with doxorubicin (DOX)
increased in a dose-dependent manner the percentage of apoptosis in NHL
cells. Coculture with irradiated L cells expressing CD40L (CD40L L
cells), but not CDw32 (CDw32 L cells), significantly reduced (33% to
89%) the percentage of apoptosis in all five cell lines treated with
0.1 to 0.5 µg/mL of DOX, but in only three cell lines at 1 µg/mL.
Interleukin-10 (IL-10), IL-6, IL-2, or tumor necrosis factor (TNF)
induced no additive protective effects with CD40L L cells. In all five
cell lines, DOX induced a concentration-dependent increase of the
activity of the cysteine-protease caspase 3. Coculture with CD40L L
cells, but not with CDw32 L cells, inhibited (38% to 100%) the
activation of caspase 3 induced by 0.1 to 0.5 µg/mL of DOX in all
five NHL cell lines, but in only two cell lines at 1 µg/mL. Finally,
the antiproliferative effect of 0.1 to 0.5 µg/mL concentrations of
DOX was also partially abrogated on coculture with CD40L L cells in all
five cell lines, but in only two cell lines at 1 µg/mL. Cytokines,
either alone or in combination with CD40L L cells, did not affect
DOX-induced inhibition of proliferation. These results indicate that
CD40L inhibits the apoptosis and antiproliferative effect induced by
DOX and interferes with caspase 3 activation in B NHL cell lines.
© 1998 by The American Society of Hematology.
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