Format

Send to

Choose Destination
Front Immunol. 2019 Dec 10;10:2876. doi: 10.3389/fimmu.2019.02876. eCollection 2019.

Role of Tumor-Mediated Dendritic Cell Tolerization in Immune Evasion.

Author information

1
Division of Medical Oncology, Department of Medicine, Duke Cancer Institute, Durham, NC, United States.
2
Department of Pharmacology and Cancer Biology, Duke University, Durham, NC, United States.

Abstract

The vast majority of cancer-related deaths are due to metastasis, a process that requires evasion of the host immune system. In addition, a significant percentage of cancer patients do not benefit from our current immunotherapy arsenal due to either primary or secondary immunotherapy resistance. Importantly, select subsets of dendritic cells (DCs) have been shown to be indispensable for generating responses to checkpoint inhibitor immunotherapy. These observations are consistent with the critical role of DCs in antigen cross-presentation and the generation of effective anti-tumor immunity. Therefore, the evolution of efficient tumor-extrinsic mechanisms to modulate DCs is expected to be a potent strategy to escape immunosurveillance and various immunotherapy strategies. Despite this critical role, little is known regarding the methods by which cancers subvert DC function. Herein, we focus on those select mechanisms utilized by developing cancers to co-opt and tolerize local DC populations. We discuss the reported mechanisms utilized by cancers to induce DC tolerization in the tumor microenvironment, describing various parallels between the evolution of these mechanisms and the process of mesenchymal transformation involved in tumorigenesis and metastasis, and we highlight strategies to reverse these mechanisms in order to enhance the efficacy of the currently available checkpoint inhibitor immunotherapies.

KEYWORDS:

cancer immunotherapy; dendritic cell immunotherapy; dendritic cell tolerance; epithelial-to-mesenchymal transition; exosomes; immune checkpoint inhibition; metastasis; myeloid-derived suppressor cells

Supplemental Content

Full text links

Icon for Frontiers Media SA Icon for PubMed Central
Loading ...
Support Center