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Splenic Dendritic Cells Involved in Cross-Tolerance of Tumor Antigens Can Play a Stimulatory Role in Adoptive T-Cell Therapy

Gibbins, John D.*,†; Ancelet, Lindsay R.*,‡; Osmond, Taryn L.*; Petersen, Troels R.*; Hermans, Ian F.*,†,‡

doi: 10.1097/CJI.0000000000000096
Basic Studies

Circulating antigens released from tumor cells can drain into the spleen and be acquired by resident antigen-presenting cells (APCs). Here, we examined the ability of splenic dendritic cells to cross-present tumor antigens to CD8+ T cells and investigated the effects that this has on T-cell therapy in a murine model of lymphoma. In the presence of established lymphoma, langerin (CD207)-expressing CD8α+ dendritic cells acquired, processed, and cross-presented tumor antigens to naive CD8+ T cells. Although this resulted in initial T-cell proliferation, the T-cell population failed to expand measurably over the following days, and tumor-free survival was actually improved when langerin-expressing cells were depleted. In contrast, following adoptive T-cell therapy with in vitro–activated CD8+ T cells, marked antitumor activity was observed and associated with accumulation of activated antigen-specific CD8+ T cells in the spleen and blood, whereas tumor protection and T-cell accumulation were significantly reduced in animals depleted of langerin-expressing cells. Therefore, although resident APCs that acquire tumor antigens may induce tolerance in naive cells in the absence of further stimuli, they can play an important role in promoting antitumor immunity during the course of T-cell therapy. It is possible that further therapeutic benefit will result from improving the activation status of these APCs.

*Malaghan Institute of Medical Research

School of Biological Sciences, Victoria University of Wellington, Wellington

Maurice Wilkins Centre, Auckland, New Zealand

Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website, www.immunotherapy-journal.com.

J.D.G. and L.R.A. are cofirst authors.

Reprints: Ian F. Hermans, Malaghan Institute of Medical Research, P.O. Box 7060, Wellington 6242, New Zealand (e-mail: ihermans@malaghan.org.nz).

Received March 29, 2015

Accepted July 27, 2015

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