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Thursday, September 29, 2011

How immune cells lead to cancer


The study prompts a re-think of cancer therapies that aim at boosting the immune system.
Image: eraxion/iStockphoto
Scientists at A*STAR’s Singapore Immunology Network (SIgN) have shown for the first time that PMN-MDSC body’s immune system to combat cancer, a type of immune cell in the body that suppresses the immune response, can actually accelerate the growth and spread of cancerous tumours directly. This finding explains how inflammation, the body's natural defence mechanism when a tissue or an organ becomes affected, is linked to cancer progression. It also highlights the need for a careful reassessment of current cancer therapies that target the body’s immune system to combat cancer.

Using a mouse model of melanoma, one of the most aggressive types of skin cancer, Benjamin Toh, an A*STAR scholar working under the supervision of Professor Jean-Pierre Abastado, a Principal Investigator of SIgN, discovered that the primary tumour first produces a unique protein “CXCL5”. CXCL5 specifically attracts the PMN-MDSC immune cells to the primary tumour, accelerating its growth. These PMN-MDSC immune cells also reactivate an innate cellular programme in early skin growth, which causes the cancer cells to detach and spread from the primary tumour to other parts of the body. However, this migratory ability is transient; migrating cancer cells can spontaneously lose their migratory potential and form a new tumour in another site. 

Said Prof Abastado, “We are really excited because our finding is a clear mechanistic explanation for the long-recognized link between inflammation and cancer progression. It may have significant and far-reaching clinical implications in the way we treat cancer. This study will certainly prompt us to re-think about cancer therapies that aim at boosting the immune system.”

This latest finding on the cancer cells’ transient migratory ability also reinforced the team’s earlier studies which showed that cancer cells can in fact detach and migrate away from the primary tumour at a very early stage, often before the primary tumour is even detected. This challenges the current theory that cancer progression is a linear process, where the developing cancer cell sequentially accumulates mutations that give it the ability to metastasize i.e. to migrate from the primary tumour and settle in a new site to establish a new tumour. 

Prof Paola Castagnoli, Scientific Director of SIgN added, “This study has definitely opened a new area in cancer research where more specific therapeutic targets might be uncovered within our body’s immune system. It is such new knowledge discovered through fundamental research that we are able to find new strategies to combat complex clinical conditions like cancer with a more holistic and effective approach.”
The research findings described in this news release can be found in the 27 Sept 2011 issue of PLoS Biology under the title, "Mesenchymal Transition and Dissemination of Cancer Cells is driven by Myeloid-Derived Suppressor Cells infiltrating the Primary Tumour” by Benjamin Toh, Xiaojie Wang, Jo Keeble, Wen Jing Sim, Karen Khoo, Wing-Cheong Wong, Masashi Kato, Armelle Prevost-Blondel, Jean-Paul Thiery and Jean-Pierre Abastado.
Editor's Note: Original news release can be found here.

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