The Role of Type 1 Conventional Dendritic Cells in Cancer Immunity

Jan P Böttcher, Caetano Reis e Sousa, Jan P Böttcher, Caetano Reis e Sousa

Abstract

Dendritic cells (DCs) are key orchestrators of immune responses. A specific DC subset, conventional type 1 DCs (cDC1s), has been recently associated with human cancer patient survival and, in preclinical models, is critical for the spontaneous rejection of immunogenic cancers and for the success of T cell-based immunotherapies. The unique role of cDC1 reflects the ability to initiate de novo T cell responses after migrating to tumor-draining lymph nodes, as well as to attract T cells, secrete cytokines, and present tumor antigens within the tumor microenvironment, enhancing local cytotoxic T cell function. Strategies aimed at increasing cDC1 abundance in tumors and enhancing their functionality provide attractive new avenues to boost anti-tumor immunity and overcome resistance to cancer immunotherapies.

Keywords: cDC1; cancer immunity; dendritic cells; immune evasion; immunotherapy; tumor microenvironment.

Copyright © 2018 Francis Crick Institute. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1
Figure 1
Orchestration of Cancer Immune Control by cDC1. Conventional type 1 dendritic cells (cDC1s) are recruited into the tumor microenvironment by chemokines such as XCL1 and CCL5, produced by intratumoral natural killer (NK) cells (and potentially other lymphocytes). NK cells further secrete the growth factor FLT3L, which supports the survival of cDC1s and might enhance local cDC1 differentiation from DC precursors. Within the tumor, cDC1s take up material from (dead?) tumor cells and are uniquely able to transport tumor antigens to tumor-draining lymph nodes for presentation to naive CD8+ T cells, priming cytotoxic effector CD8+ T cells. In addition, cDC1s within the tumor microenvironment produce the chemokines CXCL9/10 that can recruit CD8+ effector T cells into tumor tissue and can locally present tumor antigens to restimulate recruited T cells. Finally, the anti-tumor activity of T cells and NK cells within the tumor might further be boosted by cytokines made by cDC1, for example, interleukin-12 (IL-12), that, in turn, is amplified by T- and NK cell–derived cytokines such as interferon-γ (IFN-γ).

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