Abstract
Myeloid-derived suppressor cells (MDSCs) are known to contribute to immune evasion in cancer. However, the function of the human granulocytic (G)-MDSC subset during tumor progression is largely unknown, and there are no established markers for their identification in human tumor specimens. Using gene expression profiling, mass cytometry, and tumor microarrays, we here demonstrate that human G-MDSCs occur as neutrophils at distinct maturation stages, with a disease-specific profile. G-MDSCs derived from patients with metastatic breast cancer and malignant melanoma display a unique immature neutrophil profile, that is more similar to healthy donor neutrophils than to G-MDSCs from sepsis patients. Finally, we show that primary G-MDSCs from metastatic breast cancer patients co-transplanted with breast cancer cells, promote tumor growth, and affect vessel formation, leading to myeloid immune cell exclusion. Our findings reveal a role for human G-MDSC in tumor progression and have clinical implications also for targeted immunotherapy.
Highlights
Avoidance of immune surveillance enables tumor development and is one of the hallmarks of cancer (Hanahan & Weinberg, 2011)
We first asked whether G-myeloid-derived suppressor cells (MDSCs) levels change in individuals with different malignancies compared with healthy individuals
We show that human granulocytic MDSCs (G-MDSCs) represent neutrophils at distinct maturation stages, with the surface profile specific to the host’s malignancy
Summary
Avoidance of immune surveillance enables tumor development and is one of the hallmarks of cancer (Hanahan & Weinberg, 2011). One mechanism exploited by cancer to evade immune destruction is the accumulation of immunosuppressive myeloid-derived suppressor cells (MDSCs) (Swann & Smyth, 2007). These cells are immature immunosuppressive myeloid cells that are generated in most patients with advanced cancer, causing T-cell suppression by mediators, for example, reactive oxygen species (ROS), iNOS, or arginase I. MDSCs might constitute a good target for anti-cancer therapies, but major challenges in defining their nature in humans have until now prevented specific targeting. MDSCs have been predominantly described in cancer, they are implicated in other pathological conditions, for example sepsis (Janols et al, 2014; Kontaki et al, 2017). The relationship between MDSCs in different diseases, both regarding their identity and function, remains obscure
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