Nature Medicine
8, 1433 - 1437 (2002)
Published online: 11 November 2002; Corrected online: 16 October 2002 | doi:10.1038/nm1202-797
T cells require TRAIL for optimal graft-versus-tumor activityCornelius Schmaltz1, Onder Alpdogan2, Barry J. Kappel2, Stephanie J. Muriglan2, Jimmy A. Rotolo2, Jennifer Ongchin2, Lucy M. Willis2, Andrew S. Greenberg2, Jeffrey M. Eng2, James M. Crawford3, George F. Murphy4, Hideo Yagita5, Henning Walczak6, Jacques J. Peschon7
& Marcel R.M. van den Brink21
Department of Pediatrics, Memorial Sloan−Kettering Cancer Center, New York, New York, USA
2
Department of Medicine, Memorial Sloan−Kettering Cancer Center, New York, New York, USA
3
Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, Florida, USA
4
Department of Pathology, Thomas Jefferson Medical Center, Philadelphia, Pennsylvania, USA
5
Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan
6
Division of Apoptosis Regulation, German Cancer Research Center, Heidelberg, Germany
7
Department of Molecular Immunology, Immunex, Seattle, Washington, USA
Correspondence should be addressed to Marcel R.M. van den Brink m-van-den-brink@ski.mskcc.orgTumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily that exhibits specific tumoricidal activity against a variety of tumors1,
2. It is expressed on different cells of the immune system and plays a role in natural killer cell−mediated tumor surveillance3,
4,
5. In allogeneic hematopoietic-cell transplantation, the reactivity of the donor T cell against malignant cells is essential for the graft-versus-tumor (GVT) effect6. Cytolytic activity of T cells is primarily mediated through the Fas−Fas ligand and perforin−granzyme pathways. However, T cells deficient for both Fas ligand and perforin can still exert GVT activity in vivo in mouse models7,
8. To uncover a potential role for TRAIL in donor T cell−mediated GVT activity, we compared donor T cells from TRAIL-deficient and wild-type mice in clinically relevant mouse bone-marrow transplantation models. We found that alloreactive T cells can express TRAIL, but the absence of TRAIL had no effect on their proliferative and cytokine response to alloantigens. TRAIL-deficient T cells showed significantly lower GVT activity than did TRAIL-expressing T cells, but no important differences in graft-versus-host disease, a major complication of allogeneic hematopoietic cell transplantation, were observed. These data suggest that strategies to enhance TRAIL-mediated GVT activity could decrease relapse rates of malignancies after hematopoietic cell transplantation without exacerbation of graft-versus-host disease.
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