Immune suppression in the tumor microenvironment: a role for dendritic cell-mediated tolerization of T cells

Abstract

Immune suppression remains a consistent obstacle to successful anti-tumor immune responses. As tumors develop, they create a microenvironment that not only supports tumor growth and metastasis but also reduces potential adaptive immunity to tumor antigens. Among the many components of this tumor microenvironment is a population of dendritic cells which exert profound immune suppressive effects on T cells. In this review, we discuss our recent findings related to these tumor-associated dendritic cells and how targeting them may serve to generate more durable anti-tumor immune responses.

Fig. 1

Tumor-associated dendritic cells regulate T cell responsiveness in the tumor microenvironment. a The prostatic tumor microenvironment (TME) contains a variety of inflammatory cells that contribute to immune suppression. Tumor-associated dendritic cells (TADCs) tolerize CD8⁺ T cells that enter the TME in a FOXO3-dependent mechanism. Induction of this tolerogenic behavior by TADCs may be mediated by Treg cells, mast cells, or tumor-derived factors. b Provision of tumor-specific CD4⁺ T cells alters the TME and prevents tolerization of CD8⁺ T cells. This is in part mediated by the activation of TADC and down-regulation of FOXO3 expression by TADC