Research group - Helen Kaipe

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.

Ongoing projects

Many of the ongoing projects are performed in close collaboration with other researchers at Karolinska Institutet and Karolinska University Hospital, but also at Linköping University, Göteborg University and Imperial Collage in London.

1. Placental immunology
   • Characterization of the composition and function of immune cell subsets in decidua and intervillous blood at different stages of pregnancy – specific focus on MAIT cells and T cells.
   • Placental immune cells and chemokine patterns in pregnancy complications, including preeclampsia, intrauterine growth restriction and preterm birth
   • Effects of decidual stromal cells on monocyte/macrophage differentiation and T cell function
   • Characterization of decidual stromal cells from complicated pregnancies
2. Cancer-associated fibroblasts and immune cells in pancreatic cancer
   • Interactions between cancer-associated fibroblasts and T cells in pancreatic cancer – emphasis on co-inhibitory markers and chemokine receptors
   • Means to decrease the activation of cancer-associated fibroblasts
   • Characterization and spatial distribution of MAIT cells and other T cell subsets in pancreatic tumor

Research group leader Helen Kaipe