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Location of cancer’s growth affects treatment effectiveness

Future cancer treatments may need to take into account the different locations that a cancer spreads to, because of important differences in the ability of the immune system to clear tumours growing in different parts of the body.
A new study by scientists at The Institute of Cancer Research, London, showed that mice with melanoma – which often grows just under the skin, but is also able to spread to other locations – responded differently to a viral therapy depending on where in the body their tumours developed.
Melanoma cells from under the skin expressed a different repertoire of immunogens – molecules on the cell surface that stimulate the immune system’s threat response – 

than melanomas growing in the brain. This occurred even though the tumour cells that were implanted came from the same original source.

The viral therapy was able to recognise immunogens on brain melanoma cells, leading to their destruction, but was ineffective against skin melanomas because the disease in that subsite expressed a different set of specific markers.

The researchers showed that treatment resistance of skin cancers occurred because the virus – a modified form related to the virus that causes rabies – did not recognise the different repertoire of immunogens on the cells’ surface as a threat.

They found that the viral therapy was only effective against brain or skin melanomas when it targeted the specific immunogens found on the tumours at each site, showing that tumours of the same disease may be affected by where they grow in the body.

The study, published in the journal Molecular Therapy, was supported in the UK by Cancer Research UK.

Its findings are a direct example of how different sub-populations of tumour cells within the same patient may determine the effectiveness of anti-cancer treatments, including immunotherapy.

Immunotherapy – a relatively new area in cancer treatment – uses patients’ own immune systems to target tumour cells. The team of researchers who carried out this study are developing modified viruses as a new form of immunotherapy, as well as using them to infect and kill cancer cells directly.

Other researchers at The Institute of Cancer Research are also exploring wider effects of the tumour microenvironment – where a cancer grows – on cancer’s growth and spread.

Professor Kevin Harrington, Professor of Biological Cancer Therapies at The Institute of Cancer Research, London, and honorary consultant at The Royal Marsden NHS Foundation Trust, said:

“Currently we treat cancer based largely on how it looks under the microscope and the genetic mutations it has – but our study shows that the site of a tumour’s growth can profoundly affect its make-up, and in turn which treatments will work against it.

“In mice, we found that melanoma tumours in the brain expressed a distinct set of immunogens to those expressed by melanoma tumours found under the skin, meaning that viral treatments effective against melanoma tumours in the brain were completely ineffective for melanomas under the skin,and vice versa.

“This is the first time we’ve seen how the site of a tumour can change immunogen expression in cancer. Our findings show that where in the body a tumour develops could affect how treatments like immunotherapy are administered in the future.”

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