The Dark Side of Dendritic Cells: Development and Exploitation of Tolerogenic Activity That Favor Tumor Outgrowth and Immune Escape

Barbara Seliger,Chiara Massa

doi:10.3389/fimmu.2013.00419

Barbara Seliger, Chiara Massa

Open Access

https://doi.org/10.3389/fimmu.2013.00419

Copy DOI

Abstract

Dendritic cells (DC) play a central role in the regulation of the immune responses by providing the information needed to decide between tolerance, ignorance, or active responses. For this reason different therapies aim at manipulating DC to obtain the desired response, such as enhanced cell-mediated toxicity against tumor and infected cells or the induction of tolerance in autoimmunity and transplantation. In the last decade studies performed in these settings have started to identify (some) molecules/factors involved in the acquisition of a tolerogenic DC phenotype as well as the underlying mechanisms of their regulatory function on different immune cell populations.

Highlights

The immune system evolved with the difficult task of preserving the integrity of the “self,” while protecting it from “non-self ” and/or dangerous invaders, finding the right balance between aggression and tolerance
A central role in orchestrating the different immune cell subpopulations is played by dendritic cells (DC), the major professional antigen presenting cells (APC)
DC in cancer patients can be affected in their differentiation capacity, with either enhanced apoptosis or skewed phenotype toward immature cells with suppressive properties collectively named myeloid derived suppressor cells [MDSC; [1, 2]], in their ability to process and/or present tumor-associated antigens (TAA) and in their ability to interact with effector cells, e.g., to activate and/or correctly polarize them

Summary

INTRODUCTION

The immune system evolved with the difficult task of preserving the integrity of the “self,” while protecting it from “non-self ” and/or dangerous invaders, finding the right balance between aggression and tolerance. In line with the central role of DC in balancing response versus tolerance, many of the immune escape mechanisms displayed by cancer cells affect DC. These include alterations in the frequency and/or function of circulating and tumor-infiltrating DC in patients with tumors of different histologies. MYELOID DC AND CANCER Tumor cells can influence the phenotype and function of myeloid cells at different time points of their life and with distinct mechanisms These include the metabolic shift of tumor cells toward the anaerobic glycolytic pathway for glucose degradation resulting in increased concentrations of extracellular lactate and an acidification of the microenvironment, the so-called Warburg effect [3].

APC properties

CONCLUSION