Once upon a prime: DCs shape cancer immunity

Abstract

Cytotoxic CD8⁺ T cells are potent killers of diseased cells, but their functional capacity is often compromised in cancer. The quality of antitumor T cell immunity is determined during T cell priming in the lymph node and further influenced by the local microenvironment of the tumor. Increasing evidence indicates that dendritic cells (DCs) have the capacity to precisely regulate the functional quality of antitumor T cell responses in both locations. In this review, we discuss recent advances in our understanding of how distinct DC-derived signals influence CD8⁺ T cell differentiation and antitumor functions. Insight into the mechanisms of DC-mediated regulation of antitumor immunity could inspire the development of improved approaches to prevent and reverse T cell dysfunction in cancer.

Keywords: T cell priming; antitumor immunity; cancer immunotherapy; cytotoxic T cells; dendritic cells; stimulatory signals.

Figure 1.. DCs guide T cell progression through the Cancer Immunity Cycle.

DCs initiate and support anti-tumor CD8⁺ T cell responses by (1) priming naïve tumor-reactive T cells in the tdLN, (2) recruiting activated T cells from circulation to the tumor site, (3) restimulating effector T cells within the tumor microenvironment to promote cancer cell elimination, (4) acquiring tumor-derived antigens from dying cancer cells and becoming activated, (5) migrating to the tdLN to prime new T cells and thereby restart the Cancer Immunity cycle. Created with Biorender.com.

Figure 2.. DCs provide distinct stimulatory signals to activate CD8⁺ T cells in the LN and tumor.

(Left) Migratory DCs in the tdLN prime naïve tumor-reactive CD8⁺ T cells and (right) tumor-resident DCs in the tumor microenvironment restimulate effector CD8⁺ T cell responses to promote anti-tumor immunity. In both cases, DCs can provide three distinct stimulatory signals to enable optimal T cell engagement: (1) the tumor-derived antigen presented on MHC-I, (2) costimulatory ligands, and (3) cytokines and chemokines. DCs also interact with CD4⁺ T_conv and Treg cells, which can influence DC stimulatory capacity and the resulting CD8⁺ T cell responses. Created with Biorender.com.