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SummaryAntigen presentation by host dendritic cells (DC) is critical for the initiation of adaptive immune responses. We have previously demonstrated in immunogenic routine tumor models that bone marrow (BM)-derived DC pulsed ex vivo with synthetic tumor-associated peptides, naturally expressed by tumor cells, serve as effective antitumor vaccines, protecting animals against an otherwise lethal tumor challenge (Mayordomo, J. I., T. Zorina, W.J. Storkus, C. Celluzzi, L. D. Falo, C.J. Melief, T. lldstad, W. M. Kast, A. B. DeLeo, and M. T. . Nature Med. 1:1297-1302. However, T cell-defined epitopes have not been identified for most human cancers. To explore the utility of this approach in the treatment of tumors expressing as yet uncharacterized epitopes, syngeneic granulocyte/macrophage colony-stimulating factorstimulated and BM-derived DC, pulsed with unfractionated acid-eluted tumor peptides (Storkus, W. J., H.J. Zeh III, R. D. Salter, and M. T. Lotze. 1993.J. lmmunother. 14:94-103) were used to treat mice bearing spontaneous, established tumors. The adoptive transfer of 5 3( 105 tumor peptide-pulsed DC dramatically suppressed the growth ofweaHy immunogenic tumors in day 4 to day 8 established MCA205 (H-2 b) and TS/A (H-2 a) tumor models, when applied in three biweeHy intravenous injections. Using the immunogenic C3 (H-2 b) tumor model in B6 mice, tumor peptide-pulsed DC therapy resulted in the erradication of established d14 tumors and long-term survival in 100% of treated animals. The DC-driven antitumor immune response was primarily cell mediated since the transfer of spleen cells, but not sera, from immunized mice efficiently protected sublethally irradiated naive mice against a subsequent tumor challenge. Furthermore, depletion of either CD4 + or CD8 + T cells from tumor-bearing mice before therapy totally suppressed the therapeutic efficacy of DC pulsed with tumor-derived peptides. Costimulation of the host cell-mediated antitumor immunity was critical since inoculation of the chimeric fusion protein CTLA4-Ig virtually abrogated the therapeutic effects of peptide-pulsed DC in vivo. The analysis of the cytokine pattern in the draining lymph nodes and spleens of tumor-bearing mice immunized with DC pulsed with tumor-eluted peptides revealed a marked upregulation of interleukin (IL) 4 and interferon (IFN) ~/ production, as compared with mice immunized with DC alone or DC pulsed with irrelevant peptides. DCinduced antitumor effects were completely blocked by coadministration of neutralizing monoclonal antibody directed against T helper cell 1-associated cytokines (such as IL-12, tumor necrosis factor or, IFN-~/), and eventually, but not initially, blocked by anti-raiL-4 mAb. Based on these results, we believe that DC pulsed with acid-eluted peptides derived from autologous tumors represents a novel approach to the treatment of established, weaHy imnmnogenic tumors, and serves as a basis for designing clinical trials in cancer patients.R ecent advances in the understanding of antigen presentation, antigen reco...

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Dendritic cells are antigen-presenting cells that are thought to play a major role in the antitumor immune response. The CD1a surface antigen has been shown to mediate T-cell interactions. The association between CD1a-positive peritumoral DCs and patient outcome suggests an important function for this cell population.

Summary Awns, bristle‐like structures extending from grass lemmas, provide protection against predators, contribute to photosynthesis and aid in grain dispersal. In wheat, selection of awns with minimal extension, termed awnletted, has occurred during domestication by way of loci that dominantly inhibit awn development, such as Tipped1 (B1), Tipped2 (B2), and Hooded (Hd). Here we identify and characterize the B1 gene. B1 was identified using bulked segregant RNA‐sequencing of an F2 durum wheat population and through deletion mapping of awned bread wheat mutants. Functional characterization was accomplished by gene overexpression while haplotype analyses assessed B1 polymorphisms and genetic variation. Located on chromosome 5A, B1 is a C2H2 zinc finger encoding gene with ethylene‐responsive element binding factor‐associated amphiphilic repression (EAR) motifs. Constitutive overexpression of B1 in awned wheat produced an awnletted phenotype with pleiotropic effects on plant height and fertility. Transcriptome analysis of B1 overexpression plants suggests a role as transcriptional repressor, putatively targeting pathways involved in cell proliferation. Haplotype analysis revealed a conserved B1 coding region with proximal polymorphisms and supported the contention that B1 is mainly responsible for awnletted wheats globally. B1, predominantly responsible for awn inhibition in wheat, encodes a C2H2 zinc finger protein with EAR motifs which putatively functions as a transcriptional repressor.