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Autologous tumor infiltrating T cells cytotoxic for follicular lymphoma
cells can be expanded in vitro
JL Schultze, MJ Seamon, S Michalak, JG Gribben and LM Nadler
Dana-Farber Cancer Institute and Department of Medicine, Harvard Medical
School, Boston, MA 02115, USA.
Follicular lymphomas (FLs) rarely induce clinically significant T-cell-
mediated responses. We showed that freshly isolated tumor infiltrating T
cells (T-TILs) lack tumor-specific cytotoxicity. Stimulation of these T
cells with FL cells in the presence of interleukin-2 (IL-2) and/or
costimulation via CD28 does not lead to T-cell activation and expansion. In
contrast, when stimulated with FL cells preactivated via CD40, autologous
T-TILs can be expanded by the addition of exogenous IL- 2. These T cells
can be further expanded in vitro by the addition of exogenous IL-4, IL-7,
or interferon-gamma, but not IL-12. Once activated, these T cells showed
FL-directed cytotoxicity in four of five patients tested. We concluded that
autologous cytotoxic anti-FL- specific T cells exist, but can only be
detected in vitro under optimized conditions for T-cell stimulation and
expansion. This suggests that their frequency in vivo is either very low or
that the microenvironment does not provide the necessary signals to
activate these T cells. This model system allows dissection of the
requisite conditions for activation and expansion of lymphoma-directed
cytotoxicity and may permit expansion of previously activated cytotoxic T
cells for adoptive transfer.
Volume 89,
Issue 10,
pp. 3806-3816,
05/15/1997
Copyright © 1997 by The American Society of Hematology
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