Tumor antigen processing and presentation depend critically on dendritic cell type and the mode of antigen delivery

Schnurr, M; Chen, QY; Shin, A; Chen, WS; Toy, T; Jenderek, C; Green, S; Miloradovic, L; Drane, D; Davis, ID; Villadangos, J; Shortman, K; Maraskovsky, E; Cebon, J

Author(s): Schnurr, M; Chen, QY; Shin, A; Chen, WS; Toy, T; Jenderek, C; Green, S; Miloradovic, L; Drane, D; Davis, ID; Villadangos, J; Shortman, K; Maraskovsky, E; Cebon, J;
Details: Publication Year 2005-03-15,Volume 105,Issue #6,Page 2465-2472
Journal Title: BLOOD
Publication Type: Journal Article
Abstract: Dendritic cells (DCs) are being evaluated for cancer immunotherapy due to their unique ability to induce tumor-directed T-cell responses. Here we report that the type of human DC, the mode of activation, and the strategy for delivery of antigen are 3 critical factors for efficient stimulation of tumor-specific CD8(+) and CD4(+) T cells. Only CD1c(+) blood DCs and monocyte-derived DCs (MoDCs) were capable of presenting epitopes of the full-length tumor antigen NY-ESO-1 on both major histocompatibility complex (MHC) class I (cross-presentation) and MHC II, whereas plasmacytoid DCs were limited to MHC II presentation. Cross-presentation was inefficient for soluble protein, but highly efficient for antigen-antibody immune complexes (NY-ESO-1/IC) and for protein formulated with ISCOMATRIX adjuvant (NY-ESO-1/IMX). DC activation with CD40L further enhanced cross-presentation effeciency. The mode of antigen delivery was found to be a determining factor for cytosolic proteolysis by DCs. Immune complexes (ICs) targeted a slow, proteasome-dependent cross-presentation pathway, whereas ISCOMATRIX (IMX) targeted a fast, proteasome-independent pathway. Both cross-presentation pathways resulted in a long-lived, T-cell stimulatory capacity, which was maintained for several days longer than for DCs pulsed with peptide. This may provide DCs with ample opportunities for sensitizing tumor-specific T cells against a broad array of tumor antigen epitopes in lymph nodes. (c) 2005 by The American Society of Hematology.
Publisher: AMER SOC HEMATOLOGY
Keywords: MHC CLASS-I; CD8(+) T-CELL; CROSS-PRESENTATION; ISCOMATRIX ADJUVANT; PHYSIOLOGICAL STIMULI; MIGRATORY CAPACITY; EXOGENOUS ANTIGENS; MELANOMA PATIENTS; NY-ESO-1 PROTEIN; IMMUNE-RESPONSE
Publisher's Version: https://doi.org/10.1182/blood-2004-08-3105
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Creation Date: 2005-03-15 12:00:00