During pregnancy, major physiological changes occur that include inflammation and reduced immunity, conditions that are both implicated in promoting tumor growth. Tumors are indeed more aggressive during pregnancy and have greater metastatic proclivity. To gain insight into the mechanisms that may render pregnancy permissive for tumor growth, we addressed the biological and functional properties of myeloid-derived suppressor cells (MDSC), a heterogeneous population of hematopoietic cells of variable plasticity and immunoregulatory properties, during mouse and human gestation.
Gene expression profiling of mouse MDSC has been shown to differ in pregnant and virgin mice, and the gene expression profile of pregnant animal-derived MDSC bears similarity to that observed in MDSC of tumor bearing mice. Common induced genes include Fibronectin1 and Olfactomedin4, which are known to be involved in extracellular matrix remodeling and tissue permissiveness to tumor cell implantation.
In human pregnancy, CD33+ myeloid cells isolated from peripheral blood mononuclear cells (PBMC) are shown to be more strongly inhibitory of T cell proliferation in pregnant than in non-pregnant women. We also observed reduced natural killer cell numbers in the circulation of pregnant women, but which was not linked to a decrease in their cytotoxic activity, even after co-culture with CD33+ PBMC.
Our observations suggest that mouse MDSC, as well as human CD33+ cell populations that arise during the physiological state of gestation, mimic tumor progression-associated MDSC and participate in the constitution of a permissive soil, often referred to as the pre-metastatic niche.