Submitted April 4, 2002
Accepted August 11, 2002
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*
Maisonneuve-Rosemont Hospital, Guy-Bernier Research Center, Montreal, PQ, Canada
* Corresponding author; email: c.perreault{at}videotron.ca.
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 congeneic 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 recipients' bone marrow was EL4-dependent and its kinetics was different from that observed in the recipients' spleen. We conclude that strategies need to 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.
