Objective
The stimulatory NKG2D lymphocyte receptor expressed on natural killer cells and T cells and its tumor-associated ligands enable the immune system to recognize and destroy cancer cells. This role of NKG2D is well recognized and efforts are underway to target NKG2D and its ligands for cancer therapy. However, cancers adopt diverse strategies to safeguard their survival. With advanced human cancers, NKG2D ligand expression favors tumor progression, which has been ascribed to ligand-induced immune evasion. In a surprising conceptual twist, Dr. Spies’ laboratory at the Fred Hutchinson Cancer Research Center has found that cancer cells themselves express NKG2D together with its DAP10 signaling adaptor. Above-threshold expression of NKG2D–DAP10 in ligand-bearing tumor lines activates oncogenic signaling cascades and induces differentiation changes characteristic of the epithelial-mesenchymal transition (EMT), a cellular reprogramming process that leads to increased cancer cell motility and metastatic dissemination. Intertwined with EMT is the generation of self-renewing cancer stem cells (CSCs), which are main culprits of failed cancer therapies. These findings challenge current concepts as cancer cells may co-opt NKG2D as an oncoprotein serving their own benefit.
In a preliminary assessment, this role is supported by significant correlations between proportions of cancer cells that are positive for surface NKG2D and criteria of tumor progression. This proposal seeks to establish that cancer cell NKG2D has a major role in the development of CSCs. The experimental approach involves tissue culture-based studies using model tumor cell lines and functional testing of patient-derived NKG2D bearing CSCs for their tumor forming capacity in a mouse model. The results may have profound biomedical implications by establishing a previously unrecognized mechanism that promotes tumor autonomy, and may impact translational approaches targeting NKG2D or its ligands for cancer therapy.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences basic medicine immunology
- medical and health sciences medical biotechnology cells technologies stem cells
- medical and health sciences clinical medicine oncology
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-2012-IOF
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Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
8010 GRAZ
Austria
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.