Biology Reference
In-Depth Information
309
FIGURE 14.2
Schematic of the mechanisms of graft-versus-leukemia/tumor (GVL/GVT) effects of allogeneic stem cell transplantation. Both CD4 and CD8 T cells as well
as B cells that recognize alloantigens play roles in GVL/GVT. When these antigens are minor histocompatibility antigens polymorphic between host and donor and thus
present on tumor cells as well as host tissues and organs, the result is GVL/GVT and GVHD. Targeting of polymorphic antigens between host and donor that are specific
to hematopoietic cells, however, results in the achievement of full donor chimerism and GVL/GVT without GVHD. Finally, the development of donor T- and B-cell responses
to tumor-specific antigens also results in GVL/GVT without GVHD.
exploited to improve the safety and efficacy of stem cell transplantation.
The remainder of this section outlines what is known about the biology of
the GVL/GVT effect of ASCT.
T cells and the graft-versus-tumor effect
Both CD4 and CD8 T cells appear to be necessary for a GVL/GVT effect in
mouse models. Depletion of CD4 T cells from the stem cell graft results in
decreased rates of GVHD but increased rates of relapse, whereas CD8 deple-
tion results in only increased rates of relapse
[97]
. Both T-cell subtypes can
exert direct cell killing effects on tumor cells, via Fas-mediated and perfo-
rin-mediated cytotoxicity, respectively
[98]
. In addition, CD4 T cells elabo-
rate cytokines such as IL-2, IFN-γ, and TNF-α, which can recruit additional
cytotoxic and inflammatory immune cells to enhance tumor cell killing.
When the cytotoxic activity of T lymphocytes was assessed against recipi-
ent lymphocytes and leukemia cells before (donor T cells from the donor)
and after (presumed donor T cells from the recipient) transplantation, there
was a notable gain in cytotoxicity against leukemia cells only after trans-
plantation, and this directly and inversely correlated with the incidence of
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