Exploring how tumour cells are recognised by Natural Killer cells

Lead researcher

Prof Jamie Rossjohn, Prof Andrew Brooks

Prof Jamie Rossjohn, Prof Andrew Brooks

Institution

Monash University

Tumour type:

Leukaemia, Lymphoma and Haematological malignancies

Years funded

2016-2018

Project description

Our project, focused on tumour immunology, aims to understand the mechanisms by which tumour cells are recognised and eliminated by the immune system. We will investigate one aspect of this process that is mediated by natural killer (NK) cells. The detection and elimination of tumour cells by NK cells is dictated by recognition of tumour-expressed proteins (HLA-I) by members of the killer cell immunoglobulin-like receptor (KIR) family.

We want to provide insights into the extent to which NK cells exert immune pressure on cancers. 

What is the need? 

Variation in NK receptor genes impacts on the outcome of the treatment of haematological malignancies. However, there is still no clear understanding of which NK/HLA combinations result in improved patient outcomes. Our aim is to provide valuable data that can be used to better define these clinical relationships and ultimately to improve donor selection for bone marrow transplantation.

What impact will this research have?

The research will provide valuable data that can be used to better define clinical relationships and ultimately to improve donor selection for bone marrow transplantation. These findings not only have significance for understanding how NK cells act in the context of haematological malignancy, but may also identify HLA-C allotypes for which expression is sustained over the course of disease.

This would have implications for peptide-based vaccine approaches. 

Project timeline

20162017 2018 

   Production of NK clines and assess their capacity.

Structural determination and staining of primary tumour samples.  

   Functional assessment, structural refinement and analyses.

Generation of mutant HLA tetramers and binding assays to KIR transfected cells, staining of primary tumour samples with mAbs and KIR tetramers. 

Data analyses and manuscript preparation.

 

"Our aim is to provide valuable data that can be used to better define these clinical relationships and ultimately to improve donor selection for bone marrow transplantation."