Chemokines and graft-versus-host disease - Immune Biology of Allogeneic Hematopoietic Stem Cell Transplantation - page 414

each stage of GVHD by (1) facilitating hematopoietic stem cell homing, (2)
enhancing immune cell activation and differentiation, and (3) orchestrat-
ing the recruitment of effector lymphocytes, monocytes, and neutrophils to
GVHD target organs ( Figure 17.2 ). The ability to discern a dominant role for
a particular chemokine receptor or its ligands in the induction and progres-
sion of GVHD may be thwarted by the complexity and redundancy of the
accompanying immune response. In addition, inflammation engendered
in experimental models using lethal TBI can (and often does) significantly
influence the kinetics, intensity, and scope of target organ involvement of
GVHD. Clearly, additional studies need to be completed in order to (1) draw
definitive conclusions about the role of chemokines in GVHD and (2) help
decipher the paradoxical findings reported after inhibition of these proteins
in experimental models. These issues not withstanding, it is anticipated
that future clinical trials will build upon the growing body of preclini-
cal and early-phase clinical data to determine whether specific aspects of
chemokine biology can explain the unusual cluster of GVHD target organs
and be exploited (via interruption of specific receptor:ligand interactions)
to successfully modulate the deleterious effects of GVHD while preserving
beneficial GVT responses when allogeneic HCT is employed as a curative
therapeutic option for patients with cancer.

419

Acknowledgments
The authors' work is supported in part by NIH Grants R01CA166794-01 (J.S.S.), R56AI064363
(J.S.S.), and 5 R01 HL072258 (K.R.C.) and by a grant from the Leukemia and Lymphoma Society
(J.S.S.).

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