Human Tumor-Infiltrating Dendritic Cells: From in Situ Visualization to High-Dimensional Analyses

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.

BDCA1+ cDC2s, BDCA2+ pDCs and BDCA3+ cDC1s reveal distinct pathophysiologic features and impact on clinical outcomes in melanoma patients

“…Our multi-parametric flow cytometry approach is complementary of other studies mostly investigating DC subsets in cancer patients based on in situ characterisation of DCs by immunohistochemistry or high dimensional technologies such as CyTOF and transcriptomic signatures of DC subsets. 23,24,28 The levels of circulating cDCs were shown to correlate with melanoma activity as their persistent defect reflected high risk of tumor recurrence 24 and the abundance of cDC2s relative to Treg predicted survival. 32 A negative prognostic impact of cDC2 infiltration has been also highlighted in lung cancer.…”

Crosstalk Between Innate and T Cell Adaptive Immunity With(in) the Muscle

“…Depending on the tissue, the pathogen and the microenvironment, DCs promote a specific and adequate immune response toward Th1, interferon-γ (IFN-γ) secreting T lymphocytes, or other T cell phenotypes like Th2, Th17, or even Treg lymphocytes. Moreover, DCs play a crucial role in activating CD4 + and CD8 + T cells, B lymphocytes (toward autoantibody production), as well as providing different patterns of cytokine secretion depending on the environment and stimulus they receive (Hubert et al, 2019). Using a murine model of muscle regeneration, it was demonstrated that MHCII + DCs and macrophages are present within uninjured muscle, and after a transverse crush injury in both anterior tibialis muscle, those cells increased and remained high until day 6 (Pimorady- Esfahani et al, 1997).…”

“…IIMs are characterized by high levels of circulating cytokines and chemokines, as well as by inflammatory cellular infiltrates, including macrophages, DCs, CD8 + T cells (predominantly affecting the endomysium in polymyositis) and CD4 + T cells, which affect the perimysium in dermatomyositis (Wiendl et al, 2005;Huang et al, 2018). Although the involvement of DCs has been reported in IIMs (Greenberg, 2007;Greenberg et al, 2007;Wirsdörfer et al, 2016;Hubert et al, 2019), their exact role has not yet been defined.…”

Prognostic Value and Potential Immunoregulatory Role of SCARF1 in Hepatocellular Carcinoma

“…To explore the cell-specific expression of SCARF1 within HCC tumors, we correlated the gene expression of the scavenger receptor superfamily with a number of gene sets known to be expressed in tumor-associated cell populations (41)(42)(43)(44). Interestingly, of the entire scavenger receptor superfamily, SCARF1 demonstrated the most endothelial-specific signature within HCC tumor tissues, exhibiting low to moderate correlations with the majority of the other cell type gene sets ( Figure 4A).…”