Biology and therapeutic exploitation of T cells
Introduction
T cells are potent transplantation products for the treatment of cancer, both to help eradicate tumor cells and for adjuvant therapy. Different types of T cells exist. At the polar extremes are effector T cells, which can be employed to enhance immunity to cancer and regulatory T cells, which impede anti-tumor responses, but can mitigate graft versus host disease after allogeneic stem cell transplantation. Optimal clinical implementation of T cells requires thorough understanding of both cell types.
We have the following goals:
- To enhance our fundamental understanding of the signals governing these types of T cells.
- To develop new transplantation-ready products for implementation in the clinic.
Highlights
We have characterized a novel class of memory T cells (Tissue resident memory T cells-Trm) from the human lung mucosa (Hombrink, Nature Immunology 2016, doi: 10.1038/ni.3589; NRC Handelsblad Oct. 29th 2016). These cells are necessary for optimal immune memory against respiratory infections. Given the preference of Trm to reside in epithelial tissues, these cells may, furthermore, be particularly well suited for immunity against tumors, many of which are of epithelial origin. In our study, we discovered that Trm are poised for rapid effector function, but at the same time subjected to multiple inhibitory mechanisms to allow swift reactivity without eliciting unnecessary immunopathology. Furthermore, we have identified a molecular pathway responsible for their persistence in the tissue. We believe that a molecular definition of this cell type and the regulatory mechanisms controlling these cells will help mobilize this cell type in the fight against cancer.
Funding
- PPOC grant (internal funding in competition), together with Dr. I. Jedema (LUMC), Sanquin
- LSBR grant (Landsteiner Foundation)
- PPOC grant (internal funding in competition), together with Dr. M. Wolkers, R. Spaapen, D. Thijssen, Sanquin
- NWO ZonMW TOP grant, together with Dr. J. Borst and R. van Lier
- PPOC grant (internal funding in competition), together with Dr. R. van Lier, Sanquin
- Nederlands Astma Fonds grant together with Dr. R. Hendriks,
