Abstract：
:Myeloid-derived suppressor cells (MDSCs) are immune cells that exert immunosuppression within the tumor, protecting cancer cells from the host's immune system and/or exogenous immunotherapies. While current research has been mostly focused in countering MDSC-driven immunosuppression, little is known about the mechanisms by which MDSCs disseminate/infiltrate cancerous tissue. This study looks into the use of microtextured surfaces, coupled with in vitro and in vivo cellular and molecular analysis tools, to videoscopically evaluate the dissemination patterns of MDSCs under structurally guided migration, at the single-cell level. MDSCs exhibited topographically driven migration, showing significant intra- and inter-population differences in motility, with velocities reaching ~40 μm h-1. Downstream analyses coupled with single-cell migration uncovered the presence of specific MDSC subpopulations with different degrees of tumor-infiltrating and anti-inflammatory capabilities. Granulocytic MDSCs showed a ~≥3-fold increase in maximum dissemination velocities and traveled distances, and a ~10-fold difference in the expression of pro- and anti-inflammatory markers. Prolonged culture also revealed that purified subpopulations of MDSCs exhibit remarkable plasticity, with homogeneous/sorted subpopulations giving rise to heterogenous cultures that represented the entire hierarchy of MDSC phenotypes within 7 days. These studies point towards the granulocytic subtype as a potential cellular target of interest given their superior dissemination ability and enhanced anti-inflammatory activity.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Duarte-Sanmiguel S,Shukla V,Benner B,Moore J,Lemmerman L,Lawrence W,Panic A,Wang S,Idzkowski N,Guio-Vega G,Higuita-Castro N,Ghadiali S,Carson WE,Gallego-Perez Ddoi
10.1038/s41598-020-57941-8subject
Has Abstractpub_date
2020-01-27 00:00:00pages
1189issue
1issn
2045-2322pii
10.1038/s41598-020-57941-8journal_volume
10pub_type
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