Research group - Helen Kaipe
We are interested in the immune regulatory functions in the human placenta during pregnancy and in the tumor stromal microenvironment. Our primary aim is to understand how stromal tissues affect T cells and MAIT cells during pregnancy and in cancer.
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.
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.
- 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
- 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
- Multicolor flow cytometry
- Cell culture
- Migration assays
- Cell separation from tissues
- Fluorescence microscopy
The Swedish Research Council, The Swedish Cancer Foundation, The Foundation for Childhood Cancer, The Cancer Foundation in Stockholm, Stockholm County
Programme in Biomedical Laboratory Science, Immunology courses I and II, Master's/Bachelor’s Degree Programme in Biomedicine, Medical students
Human Pancreatic Carcinoma-Associated Fibroblasts Promote Expression of Co-inhibitory Markers on CD4+ and CD8+ T-Cells.
Gorchs L, Fernández Moro C, Bankhead P, Kern KP, Sadeak I, Meng Q, et al
Front Immunol 2019 ;10():847
Recruitment of MAIT Cells to the Intervillous Space of the Placenta by Placenta-Derived Chemokines.
Solders M, Gorchs L, Tiblad E, Gidlöf S, Leeansyah E, Dias J, et al
Front Immunol 2019 ;10():1300
Mucosal-Associated Invariant T Cells Display a Poor Reconstitution and Altered Phenotype after Allogeneic Hematopoietic Stem Cell Transplantation.
Solders M, Erkers T, Gorchs L, Poiret T, Remberger M, Magalhaes I, et al
Front Immunol 2017 ;8():1861
Maternal Adaptive Immune Cells in Decidua Parietalis Display a More Activated and Coinhibitory Phenotype Compared to Decidua Basalis.
Solders M, Gorchs L, Gidlöf S, Tiblad E, Lundell AC, Kaipe H
Stem Cells Int 2017 ;2017():8010961
MAIT cells accumulate in placental intervillous space and display a highly cytotoxic phenotype upon bacterial stimulation.
Solders M, Gorchs L, Erkers T, Lundell AC, Nava S, Gidlöf S, et al
Sci Rep 2017 07;7(1):6123
IFN type I and II induce BAFF secretion from human decidual stromal cells.
Lundell AC, Nordström I, Andersson K, Lundqvist C, Telemo E, Nava S, et al
Sci Rep 2017 01;7():39904
Frontline Science: Placenta-derived decidual stromal cells alter IL-2R expression and signaling in alloantigen-activated T cells.
Erkers T, Solders M, Verleng L, Bergström C, Stikvoort A, Rane L, et al
J. Leukoc. Biol. 2017 03;101(3):623-632