(Press-News.org) Hot on the TRAIL of graft vs. host disease
For patients with leukemia and other hematological malignancies, transplantation of hematopoietic stem cells (HSCT) can be a powerfully effective therapy. In addition to the desirable anti-tumor effect, transplanted cells can also attack the host tissue, resulting in graft-versus-host disease (GVHD). In this issue of the Journal of Clinical Investigation, Arnab Ghosh and colleagues at Memorial Sloan-Kettering Cancer Center found that expression of a protein that causes cell death, TRAIL, in transplanted cells was critical for an effective anti-tumor response. Immune cells engineered to express higher levels of TRAIL killed the cells that cause GVHD and increased anti-tumor activity. In an accompanying commentary, Nelson Chao suggests that new therapeutics may take advantage of TRAIL-expressing cells to promote an anti-tumor response without putting patients at risk for GVHD.
TITLE: Fratricidal TRAIL+T cells suppress GVHD and augment anti-tumor activity after bone marrow transplantation
AUTHOR CONTACT:
Arnab Ghosh
Memorial Sloan-Kettering Cancer Center, New York, , USA
Phone: 646-888-2317; E-mail: ghosha1@mskcc.org
View this article at: http://www.jci.org/articles/view/66301?key=66e50de3cd0d7e99a4d8
ACCOMPANYING COMMENTARY
TITLE: Blazing a new TRAIL in hematopoietic cell transplantation
AUTHOR CONTACT:
Nelson J. Chao
Duke University Medical Center, Durham, NC, USA
Phone: 919-668-1011; Fax: 919-668-1091; E-mail: chao0002@mc.duke.edu
View this article at: http://www.jci.org/articles/view/69909?key=43f0101604c8f6bb12da
Researchers identify signals that direct the immune system to reject a transplanted organ
Organ transplant rejection occurs when the transplant recipient's immune system identifies the transplanted organ as foreign tissue and attacks it. It was previously thought that T cells, the immune cells that mediate rejection, must first be activated by molecules known as chemokines in order to migrate to the transplanted organ. In this issue of the Journal of Clinical Investigation, Fadi Lakkis and colleagues at the University of Pittsburgh used mice to demonstrate that chemokine stimulation of T cells is not required for migration. Instead, these cells must come into contact with immune-stimulating proteins (antigens) that are specifically expressed by the transplanted organ. In an accompanying commentary, Terry Strom discusses how these findings could have important implications for the design of novel anti-rejection therapeutics.
TITLE: Cognate antigen directs CD8+ T cell migration to vascularized transplants
AUTHOR CONTACT:
Fadi G. Lakkis
Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA
Phone: 412 383-5774; Fax: 412-383-9990; E-mail: lakkisf@upmc.edu
View this article at: http://www.jci.org/articles/view/66722?key=5debbc8dd29fc8e22b12
ACCOMPANYING COMMENTARY
TITLE: Transplant rejection and paradigms lost
AUTHOR CONTACT:
Terry Strom
Beth Israel Deaconess Medical Center, Boston, MA, USA
Phone: 1-617-735-2880; Fax: 1 617 667-0923; E-mail: tstrom@bidmc.harvard.edu
View this article at: http://www.jci.org/articles/view/69385?key=ee127335912183bcc713
ALSO IN THIS ISSUE
TITLE: Safe TNF-based antitumor therapy following p55TNFR reduction in intestinal epithelium
AUTHOR CONTACT:
George Kollias
Biomedical Sciences Research Centre (BSRC) "Alexander FLEMING", Institute o, Vari, GRC
Phone: 00302109656507; E-mail: kollias@fleming.gr
View this article at: http://www.jci.org/articles/view/65624?key=95dcd1ab2462f49889fd
TITLE: Lamin B1 mediates cell-autonomous neuropathology in a leukodystrophy mouse model
AUTHOR CONTACT:
Ying-Hui Fu
University of California San Francisco, San Francisco, CA, USA
Phone: 415-502-5614; E-mail: Ying-hui.fu@ucsf.edu
View this article at: http://www.jci.org/articles/view/66737?key=16236a3ef2fb14130105
TITLE: PD-L1 blockade synergizes with IL-2 therapy in reinvigorating exhausted T cells
AUTHOR CONTACT:
Rafi Ahmed
Emory University, Atlanta, GA, USA
Phone: 404-727-3571; E-mail: rahmed@emory.edu
View this article at: http://www.jci.org/articles/view/67008?key=331ea19f479943e34a83
TITLE: The genomic landscape of small intestine neuroendocrine tumors
AUTHOR CONTACT:
Andreas Beutler
Mayo Clinic Rochester, Rochester, MN, USA
Phone: 507 2848009; E-mail: beutler.andreas@mayo.edu
View this article at: http://www.jci.org/articles/view/67963?key=946338907594d6d91dfd
TITLE: Specific peripheral B cell tolerance defects in patients with multiple sclerosis
AUTHOR CONTACT:
Eric Meffre
Yale University School of Medicine, New Haven, CT, USA
Phone: 1-203-737-4535; Fax: 1-203-785-7903; E-mail: eric.meffre@yale.edu
View this article at: http://www.jci.org/articles/view/68775?key=e407c6c0d214181b9fad
INFORMATION: END
VIDEO:
Human ESCs generated from SCNT embryos were capable of differentiating into a variety of cell and tissue types including contracting heart cells.
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PITTSBURGH, May 15, 2013 – Transplant researchers at the University of Pittsburgh School of Medicine challenge a long-held assumption about how biologic pathways trigger immune system rejection of donor organs in a report published online today in the Journal of Clinical Investigation. Their study, sponsored by the National Institutes of Health, suggests a different paradigm is needed to develop better anti-rejection therapies.
Immune system troops called T-cells migrate to transplanted organs, fighting the foreign tissue, explained senior author Fadi Lakkis, M.D., Frank ...
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