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Antigen Processing and MHC-II Presentation by Dermal and Tumor-Infiltrating Dendritic Cells¹

Center for Immunology, University of Minnesota, Minneapolis, MN 55455

MHC-II presentation by dendritic cells (DC) is necessary both for initial priming of CD4 T cells and for induction of peripheral effector function. Although CD4 T cells can be critical for competent immunization-mediated cancer immunosurveillance, unmanipulated CD4 T cell responses to poorly immunogenic tumors result in either complete ignorance or tolerance induction, suggesting inadequate DC function. In this study, we investigated the phenotype, Ag uptake, and MHC-II presentation capacity of normal dermal DC and tumor-infiltrating DC (TIDC) in both lymphoid and peripheral sites. We found that murine tumors were extensively infiltrated by partially activated TIDC that closely resembled dermal DC by surface marker expression. However, in contrast to dermal DC, TIDC were inefficient at MHC-II presentation due to poor intrinsic protein uptake capability. This resulted in both inferior initiation of T cell responses in the draining lymph node and poor peripheral effector cell accumulation. In addition, TLR stimulation selectively enhanced MHC-II presentation of Ag by dermal DC, but not TIDC in the draining lymph node, and did not affect overall peripheral Ag uptake of either. These results show that TIDC are functionally distinct from normal interstitial DC, thus indicating that neoplastic tissues can evade effector CD4 T cells through modification of DC competence.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grants AI34824 (to M.F.M.), CA82596 (to M.F.M.), and NCI 2 T32 CA009138-31 (to M.Y.G.).

² Address correspondence and reprint requests to Dr. Matthew F. Mescher, Laboratory, Medicine and Pathology, Mayo Mail Code 334, 420 Delaware Street SE, Minneapolis, MN 55455. E-mail address: mesch001{at}umn.edu

³ Abbreviations used in this paper: DLN, draining lymph node; cRPMI, complete RPMI 1640 medium; DC, dendritic cell; FSC, forward light scatter; i.t., intratumoral; LN, lymph node; MFI, mean fluorescence intensity; TIDC, tumor-infiltrating DC.