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Pre-B acute lymphoblastic leukemia cells may induce T-cell anergy to
alloantigen
AA Cardoso, JL Schultze, VA Boussiotis, GJ Freeman, MJ Seamon, S Laszlo, A Billet, SE Sallan, JG Gribben and LM Nadler
Division of Hematologic Malignancies and Pediatric Oncology, Dana- Farber
Cancer Institute, Boston, MA 02115, USA.
Even if neoplastic cells express tumor associated antigens they still may
fail to function as antigen presenting cells (APC) if they lack expression
of one or more molecules critical for the induction of productive immunity.
These cellular defects can be repaired by physiologic activation,
transfection, or fusion of tumor cells with professional APC. Although such
defects can be repaired, antitumor specific T cells may still fail to
respond in vivo if they may have been tolerized. Here, human pre-B cell
acute lymphoblastic leukemia (pre-B ALL) was used as a model to determine
if primary human tumor cells can function as alloantigen presenting cells
(alloAPC) or alternatively whether they induce anergy. In the present
report, we show that pre-B cell ALL express alloantigen and adhesion
molecules but uniformly lack B7-1 (CD80) and only a subset express B7-2
(CD86). Pre-B ALL cells are inefficient or ineffective alloAPC and those
cases that lack expression of B7-1 and B7-2 also induce alloantigen
specific T- cell unresponsiveness. Under these circumstances, T-cell
unresponsiveness could be prevented by physiologic activation of tumor
cells via CD40, cross-linking CD28, or signaling through the common gamma
chain of the interleukin-2 receptor on T cells. Taken together, these
results suggest that pre-B ALL may be incapable of inducing clinically
significant T-cell-mediated antileukemia responses. This defect may be not
only due to their inability to function as APC, but also due to their
potential to induce tolerance. Attempts to induce clinically significant
antitumor immune responses may then require not only mechanisms to repair
the antigen presenting capacity of the tumor cells, but also reversal of
tolerance.
Volume 88,
Issue 1,
pp. 41-48,
07/01/1996
Copyright © 1996 by The American Society of Hematology
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