Myeloid-derived suppressor cells are implicated in regulating permissiveness for tumor metastasis during mouse gestation

Abstract

Metastasis depends on the ability of tumor cells to establish a relationship with the newly seeded tissue that is conducive to their survival and proliferation. However, the factors that render tissues permissive for metastatic tumor growth have yet to be fully elucidated. Breast tumors arising during pregnancy display early metastatic proclivity, raising the possibility that pregnancy may constitute a physiological condition of permissiveness for tumor dissemination. Here we have shown that during murine gestation, metastasis is enhanced regardless of tumor type, and that decreased NK cell activity is responsible for the observed increase in experimental metastasis. Gene expression changes in pregnant mouse lung and liver were shown to be similar to those detected in premetastatic sites and indicative of myeloid cell infiltration. Indeed, myeloid-derived suppressor cells (MDSCs) accumulated in pregnant mice and exerted an inhibitory effect on NK cell activity, providing a candidate mechanism for the enhanced metastatic tumor growth observed in gestant mice. Although the functions of MDSCs are not yet understood in the context of pregnancy, our observations suggest that they may represent a shared mechanism of immune suppression occurring during gestation and tumor growth.

Immunosuppressive Myeloid Cells’ Blockade in the Glioma Microenvironment Enhances the Efficacy of Immune-Stimulatory Gene Therapy

“…To this end, we made use of Gr-1-depleting antibody. 49,50 The effect of MDSC depletion was examined in combination with immune-stimulatory TK/Flt3L gene therapy in the GL26 model harboring the surrogate tumor antigen, ovalbumin (OVA), which allowed us to monitor the generation of tumor-specific T cells using the H2K b -tetramer. Gr-1 antibody administration resulted in the depletion of CD11b + /Gr-1 + cells from the tumor, spleen, and blood of GL26 tumor-bearing animals; no effect was observed on the frequency of F4/80 + or CD11c + cells ( Figure 4A).…”

Platelets promote tumour metastasis via interaction between TLR4 and tumour cell-released high-mobility group box1 protein

“…These data suggest that TLR4 deficiency led to decreased platelet activation on tumour cell infusion. Recruitment of immune cells, such as T cells, NK cells, NKT cells and myeloid-derived suppressor cells (MDSCs) can affect the tumour burden in the lung [34][35][36][37] . Therefore, we determined the changes in the composition of immune cell subsets of splenocytes, blood and metastatic tumour foci in the lung in tumour-bearing mice.…”

Granulocytic Myeloid-Derived Suppressor Cells Accumulate in Human Placenta and Polarize toward a Th2 Phenotype

“…They are part of normal hematopoiesis but are dramatically expanded and activated in many types of cancer in humans and mice (11)(12)(13)(14) as well as under other pathological conditions such as infection (15,16), trauma (17), or transplant rejection (18,19). GR-MDSCs express the common myeloid marker CD33 and the granulocytic lineage markers CD66b or CD15 whereas they do not exhibit monocytic Ags such as CD14 and HLA-DR (10,20,21).…”