T cells have the capacity to respond to foreign antigens, including fetal HLA molecules and tumor-associated antigens. However, both during pregnancy and in cancer, T-cells can be hold back by immunosuppressive mechanisms in the placenta and the in tumor microenvironment, respectively. This can be beneficial in pregnancy since it avoids rejection of the fetus, but disadvantageous in cancer as it promotes tumor immune escape.
During pregnancy, the mother’s immune system is in direct contact with fetal tissues in the placenta. This interaction takes place in the maternal part of the placenta, the decidua, and in the intervillous space of the placenta in which maternal blood circulates to provide oxygen and nutrients to the developing fetus. The intervillous blood has not been extensively studied before. Pre-eclampsia and intrauterine growth restriction are two conditions that can cause complications during pregnancy. The underlying causes of these disorders are not fully known, but immune dysregulation is likely involved.
Fibroblasts and stromal cells have previously mainly been considered to provide tissue integrity, but it has become evident that they also play an active role in directing and controlling immune responses. We and others have previously shown that placental stromal cells have an immunoregulatory capacity and can suppress T cell responses.
Pancreatic cancer is one of the most aggressive types of cancer. It is characterized by a dense stroma with activated fibroblasts, in which tumor cells are embedded. This desmoplastic reaction is also believed to prevent T cells from entering the tumor. Cancer-associated fibroblasts have been shown to promote tumor growth, but the interactions between T-cells and cancer-associated fibroblasts is poorly understood.