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Prepublished online as a Blood First Edition Paper on August 22, 2002; DOI 10.1182/blood-2002-04-1032.
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Blood, 15 January 2003, Vol. 101, No. 2, pp. 766-770
TRANSPLANTATION
Tissue distribution of target antigen has a decisive influence on
the outcome of adoptive cancer immunotherapy
Marie-Christine Meunier,
Guillaume Roy-Proulx,
Nathalie Labrecque, and
Claude Perreault
From the Guy-Bernier Research Center,
Maisonneuve-Rosemont Hospital, Montreal, PQ, Canada.
Adoptive transfer of allogeneic T cells has unmatched efficacy to
eradicate leukemic cells. We therefore sought to evaluate in kinetic
terms interactions between T cells and allogeneic leukemic cells. T
cells primed against the model B6dom1 minor
histocompatibility antigen were adoptively transferred in irradiated
B10 (B6dom1-positive) and congenic
B10.H7b (B6dom1-negative) recipients, some of
which were also injected with EL4 leukemia/lymphoma cells
(B6dom1-positive). A key finding was that the tissue
distribution of the target epitope dramatically influenced the outcome
of adoptive cancer immunotherapy. Widespread expression of
B6dom1 in B10 recipients induced apoptosis and dysfunction
of antigen-specific T cells. Furthermore, in leukemic B10 and
B10.H7b hosts, a massive accumulation of effector/memory
B6dom1-specific T cells was detected in the bone
marrow, the main site of EL4 cell growth. The accumulation of
effector/memory cells in recipient bone marrow was EL4 dependent, and
its kinetics was different from that observed in recipient spleen. We
conclude that strategies must be devised to prevent apoptosis of
adoptively transferred T cells confronted with a high antigen load and
that local monitoring of the immune response at the site of tumor
growth may be mandatory for a meaningful assessment of the efficacy of adoptive immunotherapy.
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