Considering the large number of studies focused on myeloid-derived suppressor cells (MDSCs) to date, only a handful of well-defined relationships in human cancer have been established. The difficulty of assessing the impact of MDSCs in human cancer is partly due to the relatively small number of studies performed in humans. This is compounded in the literature by a common lack of clear indication of which species is being referred to for each characteristic described. These aspects may result in inappropriate extrapolation of animal studies to those in the human setting. This is especially the case for studies focused on investigating therapies which can be used to target MDSCs or those aimed at understanding their mechanism. Here, we attempt to rectify this by reviewing only studies on MDSC performed in humans. We survey studies which explore (1) whether MDSC levels are altered in cancer patients and if this is correlated with patient survival, (2) the so far identified mechanisms employed by MDSC to exert immune suppression, and (3) whether therapeutic agents can be used to target MDSCs by either altering their level, influencing their differentiation or inhibiting their suppressive function. Despite the fact that these studies clearly show that MDSCs are important in human cancer, the clinical employment of agents intended to target them has not yet been accomplished. We identify factors which have contributed to this and propose steps which may facilitate the translation of these therapies to the clinic in future.
BackgroundEffective therapeutic management of elderly patients with cancer, on an individual basis, remains a clinical challenge. Here, we identify novel biomarkers to assess elderly patients (≥70 years of age) with breast cancer undergoing treatment with or without chemotherapy.MethodsWe performed comprehensive geriatric assessment and measured markers sensitive to alteration in ageing, including leukocyte telomere length, CMV serostatus, levels of circulating growth factors and cytokines, and immune profiling of T cell and myeloid populations in blood before and at 3 months and 12 months after initiation of therapy, using flow cytometry.ResultsWe observed changes in immune profiles over time that were specific to patients receiving chemotherapy; these patients had elevated CD4+ T effector memory re-expressing CD45RA (TEMRA) cells and relatively lower CD8+ central memory cells at 3 months, with normalized levels after 12 months. Patients’ baseline immune profiles correlated with markers such as telomere length, cytomegalovirus (CMV) serostatus and levels of circulating cytokines. We also identified correlations between baseline immune profile and geriatric assessment, i.e. more frail patients had higher levels of granulocytic cells but lower levels of cells with suppressor phenotypes including myeloid-derived suppressor cells and regulatory T cells, although none of the examined immune populations correlated with chronological age. Importantly, immune profiles prior to therapy predicted unexpected hospitalizations in patients receiving chemotherapy.ConclusionThese findings suggest that immune profiling may represent a novel complementary approach to more accurately assess the global health status of the elderly patient with breast cancer and select the most appropriate individual treatment option.Trial registrationClinicalTrials.gov, NCT00849758. Registered on 20 February 2009.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-017-0813-x) contains supplementary material, which is available to authorized users.
Biomaterial characteristics such as surface topographies have been shown to modulate macrophage phenotypes. The standard methodologies to measure macrophage response to biomaterials are marker-based and invasive. Raman microspectroscopy (RM) is a marker-independent, noninvasive technology that allows the analysis of living cells without the need for staining or processing. In the present study, we analyzed human monocyte-derived macrophages (MDMs) using RM, revealing that macrophage activation by lipopolysaccharides (LPS), interferons (IFN), or cytokines can be identified by lipid composition, which significantly differs in M0 (resting), M1 (IFN-γ/LPS), M2a (IL-4/IL-13), and M2c (IL-10) MDMs. To identify the impact of a biomaterial on MDM phenotype and polarization, we cultured macrophages on titanium disks with varying surface topographies and analyzed the adherent MDMs with RM. We detected surface topography–induced changes in MDM biochemistry and lipid composition that were not shown by less sensitive standard methods such as cytokine expression or surface antigen analysis. Our data suggest that RM may enable a more precise classification of macrophage activation and biomaterial–macrophage interaction.
Our results highlight the potential importance of cells with mMDSC phenotypes in breast cancer, identifiable already at early stages of disease. This may provide a basis for identifying possible new therapeutic targets to enhance anti-cancer immunity.
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