Immune evasion pathways and the design of dendritic cell-based cancer vaccines

Abstract

Emerging data is suggesting that the process of dendritic cell (DC) tolerization is an important step in tumorigenesis. Our understanding of the networks within the tumor microenvironment that functionally tolerize DC function is evolving while methods for genetically manipulating DC populations in situ continue to develop. A more intimate understanding of the paracrine signaling pathways which mediate immune evasion by subverting DC function promises to provide novel strategies for improving the clinical efficacy of DC-based cancer vaccines. This will likely require a better understanding of both the antigen expression profile and the immune evasion network of the tumor and its associated stromal tissues.

Figure 1

Tumor-mediated mechanisms of dendritic cell (DC) tolerization and immune suppression. Tumor-derived soluble factors and exosomes promote DC-mediated Treg differentiation to generate an immune privileged site conducive to tumor progression. COX, cyclooxgenase; PGE2, prostaglandin E2; IDO, indoleamine 2,3-dioxygenase; RA, retinoic acid.

Figure 2

Ex vivo and in vivo DC-based vaccine protocol design based on dominant immune evasion mechanisms identified in tumor and tumor-draining lymph node (TDLN) tissues.