Host-derived CD81 dendritic cells are required for induction of optimal graft-versus-tumor responses after experimental allogeneic bone marrow transplantation

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

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25 Scopus citations

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—CD81 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 CD81 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.

Original languageEnglish
Pages (from-to)4231-4241
Number of pages11
JournalBlood
Volume121
Issue number20
DOIs
StatePublished - May 16 2013

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    Toubai, T., Sun, Y., Luker, G., Liu, J., Luker, K. E., Tawara, I., Evers, R., Liu, C., Mathewson, N., Malter, C., Nieves, E., Choi, S., Murphy, K. M., & Reddy, P. (2013). Host-derived CD81 dendritic cells are required for induction of optimal graft-versus-tumor responses after experimental allogeneic bone marrow transplantation. Blood, 121(20), 4231-4241. https://doi.org/10.1182/blood-2012-05-432872