Project Details
Projekt
Innate Lymphoid Cells in human Colorectal Cancer.
Applicant
Dr. Anna Rao
Subject Area
Immunology
Term
from 2016 to 2019
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 345504696
Colorectal cancer (CRC) is the second most common cancer in Europe, both in terms of incidence and mortality. The fact that lymphocyte infiltration of the tumour is associated with better prognosis, suggests that understanding of immunological processes in the tumour microenvironment could enable the development of new successful CRC therapies. Innate lymphoid cells (ILCs) are a recently identified type of immune cells that regulate intestinal immune responses. However, although mouse models have suggested that ILCs participate in colon tumour development, the role for ILCs in human CRC remains unknown. Through my host group, I have unique access to intestinal material from CRC patients, which I will use to address how ILCs influence CRC initiation and/or progression. To ensure the success and quality of this truly translational project, I am working closely together with gastroenterology surgeons. In this proposal I will firstly perform a detailed characterization of the ILCs in the tumorous and healthy gut mucosal tissue of CRC patients. Furthermore, to determine how ILCs act in the complex intratumoral cellular network, I will investigate the crosstalk between ILCs, tumour cells and other immune cells, primarily T lymphocyte populations. My preliminary data obtained from the CRC patient samples (so far n=22) show that there is a gradually increasing dysfunction of ILCs stretching from non-affected into the cancerous tissues. These data suggest that the tumour microenvironment might influence ILC function, causing plasticity of these cells. Therefor, I plan to perform co-cultures of ILCs with stromal cells from different sub-anatomical regions surrounding the cancerous area, with the intention of dissecting factors driving ILC plasticity. Such experiments have not been performed before, and would contribute to better understanding of ILC interactions with the tumour stroma in human colon cancer. Furthermore, data generated in the initial phase of my postdoctoral work suggests that ILCs may present cancer antigens to T cells and thus, regulate cellular immune responses in the tumour microenvironment. In the proposed project I aim to elucidate how ILCs affect adaptive anti-tumour immune responses, either promoting tumour killing, or inducing its tolerisation and progression. Knowledge arising from these studies will therefore have immense translational value and clinical implications. We hope that our findings could reveal novel potential targets for future therapeutic interventions and help in designing effective anti cancer immunotherapies and diagnostics.
DFG Programme
Research Fellowships
International Connection
Sweden
