Abstract
The interaction between tumor cells and the immune system is considered to be a dynamic process. Dendritic cells (DCs) play a pivotal role in anti-tumor immunity owing to their outstanding T cell activation ability. Their functions and activities are broad ranged, triggering different mechanisms and responses to the DC subset. Several studies identified in situ human tumor-infiltrating DCs by immunostaining using a limited number of markers. However, considering the heterogeneity of DC subsets, the identification of each subtype present in the immune infiltrate is essential. To achieve this, studies initially relied on flow cytometry analyses to provide a precise characterization of tumor-associated DC subsets based on a combination of multiple markers. The concomitant development of advanced technologies, such as mass cytometry or complete transcriptome sequencing of a cell population or at a single cell level, has provided further details on previously identified populations, has unveiled previously unknown populations, and has finally led to the standardization of the DCs classification across tissues and species. Here, we review the evolution of tumor-associated DC description, from in situ visualization to their characterization with high-dimensional technologies, and the clinical use of these findings specifically focusing on the prognostic impact of DCs in cancers.
Highlights
They represent only a very small proportion of leukocytes, dendritic cells (DCs) are central to the immune system [1]
The interaction between tumor cells and the immune system is considered to be as a dynamic process [2,3,4] and, owing to their sentinel cell properties, DCs are at the heart of early stage of tumor immune surveillance [3]
DCs are at the interface between innate and adaptive immunity through their involvement in naïve T cell priming based on their ability to sense danger signals, migrate to secondary lymphoid organs, and present antigen (Ag)
Summary
They represent only a very small proportion of leukocytes, dendritic cells (DCs) are central to the immune system [1]. Several methodologies are currently used to define the different sub-populations [6,7] They include surface phenotyping, generally performed by flow cytometry [8,9], ontogeny analysis to identify their progenitors and the transcription factors involved in their development [10,11,12,13], as well as their functional characterization [5]. High- dimensional molecular analyses have arisen, providing a comprehensive as well as an extensively detailed portrait of the tumor microenvironment, and further improving our knowledge of DC subpopulations [15,16,17] These different approaches are complementary and provide a description of DCs which is constantly evolving and sometimes controversial. We discuss the strengths and weaknesses of each approach in this field, focusing on new high-dimensional technologies and future strategies
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