Host-derived CD8+ dendritic cells are required for induction of optimal graft-versus-tumor responses after experimental allogeneic bone marrow transplantation.
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| Abstract |
The graft-versus-tumor (GVT) effect after allogeneic hematopoietic cell transplantation (allo-HCT) represents an effective form of immunotherapy against many malignancies. Meaningful separation of the potentially curative GVT responses from graft-versus-host disease (GVHD), the most serious toxicity following T-cell replete allo-HCT, has been an elusive goal. GVHD is initiated by alloantigens, although both alloantigens and tumor-specific antigens (TSAs) initiate GVT responses. Emerging data have illuminated a role for antigen-presenting cells (APCs) in inducing alloantigen-specific responses. By using multiple clinically relevant murine models, we show that a specific subset of host-derived APCs-CD8(+) dendritic cells (DCs)-enhances TSA responses and is required for optimal induction of GVT. Stimulation of TLR3, which among host hematopoietic APC subsets is predominantly expressed on CD8(+) DCs, enhanced GVT without exacerbating GVHD. Thus, strategies that modulate host APC subsets without direct manipulation of donor T cells could augment GVT responses and enhance the efficacy of allo-HCT.
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| Authors | Tomomi Toubai, Yaping Sun, Gary Luker, Jun Liu, Kathryn E Luker, Isao Tawara, Rebecca Evers, Chen Liu, Nathan Mathewson, Chelsea Malter, Evelyn Nieves, Sung Choi, Kenneth M Murphy, Pavan Reddy |
| Journal | Blood (Blood) Vol. 121 Issue 20 Pg. 4231-41 (May 16 2013) ISSN: 1528-0020 [Electronic] United States |
| PMID | 23520337 (Publication Type: Journal Article, Research Support, N.I.H., Extramural) |
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