How to measure the immunosuppressive activity of MDSC: assays, problems and potential solutions

Abstract

Myeloid-derived suppressor cells (MDSC) are a heterogeneous group of mononuclear and polymorphonuclear myeloid cells, which are present at very low numbers in healthy subjects, but can expand substantially under disease conditions. Depending on disease type and stage, MDSC comprise varying amounts of immature and mature differentiation stages of myeloid cells. Validated unique phenotypic markers for MDSC are still lacking. Therefore, the functional analysis of these cells is of central importance for their identification and characterization. Various disease-promoting and immunosuppressive functions of MDSC are reported in the literature. Among those, the capacity to modulate the activity of T cells is by far the most often used and best-established read-out system. In this review, we critically evaluate the assays available for the functional analysis of human and murine MDSC under in vitro and in vivo conditions. We also discuss critical issues and controls associated with those assays. We aim at providing suggestions and recommendations useful for the contemporary biological characterization of MDSC.

Clinical Relevance and Suppressive Capacity of Human Myeloid-Derived Suppressor Cell Subsets

“…Although functional testing is a major criterion in defining MDSC, at present, there is no consensus on the best test system, and numerous T-cell suppression assays are used and reported in the literature (23). In addition, MDSC may also inhibit natural killer cells, employing mechanisms distinct from suppression of T-cell activity (24,25).…”

Neutrophil Diversity in Health and Disease

“…The same requirement is valid for other suppressive neutrophil populations described (see main text). Current guidance for the standardization and harmonization of functional tests for suppressive cells has recently been provided [135].…”

Deciphering myeloid-derived suppressor cells: isolation and markers in humans, mice and non-human primates

“…Unfortunately, due to the differences in marker and model selection, the information available in the literature, even within one species, is highly heterogeneous and frequently conflicting observations are reported. Therefore, proper standardization of MDSC identification isolation and functional characterization are essential to guide the field [ 12 ].…”