Abstract
In most cancers, myeloid cells represent the major component of the immune microenvironment. Deciphering the impact of these cells on tumor growth and in response to various anti-tumor therapies is a key issue. Many studies have elucidated the role of tumor-associated monocytes and tumor-associated macrophages (TAM) in tumor development, angiogenesis, and therapeutic failure. In contrast, tumor dendritic cells (DC) are associated with tumor antigen uptake and T-cell priming. Myeloid subpopulations display differences in ontogeny, state of differentiation and distribution within the neoplastic tissue, making them difficult to study. The development of high-dimensional genomic and cytometric analyses has unveiled the large functional diversity of myeloid cells. Important fundamental insights on the biology of myeloid cells have also been provided by a boom in functional fluorescent imaging techniques, in particular for TAM. These approaches allow the tracking of cell behavior in native physiological environments, incorporating spatio-temporal dimensions in the study of their functional activity. Nevertheless, tracking myeloid cells within the TME remains a challenging process as many markers overlap between monocytes, macrophages, DC, and neutrophils. Therefore, perfect discrimination between myeloid subsets remains impossible to date. Herein we review the specific functions of myeloid cells in tumor development unveiled by image-based tracking, the limits of fluorescent reporters commonly used to accurately track specific myeloid cells, and novel combinations of myeloid-associated fluorescent reporters that better discriminate the relative contributions of these cells to tumor biology according to their origin and tissue localization.
Highlights
Myeloid cells form a vast and heterogeneous group of cells that play a major role in shaping the tumor microenvironment (TME)
A main hurdle of this approach rests on the accurate tracking of these cells since the number of available markers are more limited than for flow cytometry and many markers overlap between monocytes, macrophages, dendritic cells (DC) and even neutrophils, potentially leading to misinterpretations
We discuss limitations of the most common models used for the discrimination and tracking of these different subsets, and we present some perspectives derived from the combination of different fluorescent reporter mouse strains used to unveil microanatomical niches of myeloid subsets in tumors
Summary
Myeloid cells form a vast and heterogeneous group of cells that play a major role in shaping the tumor microenvironment (TME). We have developed an additional dimension of resolution using the combination of MacBlue x Cx3cr1EGFP x MacApple reporter mice This strain provides an improved display of the myeloid compartement heterogeneity in lung tumors, allowing the visualization of recruited, resident interstitial, and alveolar macrophages as well as neutrophils based on differential expression of the fluorescent reporters (Figure 1A). This further highlights microanatomical niches with specific myeloid subset distributions (Figure 1B).
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