Why some tumours evade immunotherapy

London: The absence of a particular molecule from cells can make tumours recur even after immunotherapy, a group of researchers from Germany has found.

Immunotherapy is a new and highly promising form of treatment for cancer.

A team of researchers from the Max Delbruck Center for Molecular Medicine in the Helmholtz Association (MDC) and the Berlin Institute of Health (BIH) and Charite -- Universitatsmedizin Berlin will help doctors in selecting suitable target points for immunotherapy.

One form of immunotherapy for cancer is T-cell receptor gene therapy that involves removing T-cells (a type of immune cell) from the blood and altering them in the test tube to enable them to target cancer cells.

"The tumours are not recognised by the T-cells. We want to find out how to reduce the frequency with which the cancer recurs after treatment," biologist Ana Textor said.

To achieve this, the researchers trained two different types of T-cell. One of the T-cell types permanently destroyed the tumours in a mouse model. After treatment with the other T-cell type, initial tumour regression was followed by recurrence.

The researchers found that when the tumour recurred, a particular molecule on the cell surface -- called the epitope -- was no longer present on the cell surface in sufficient quantity.

This was because the epitopes in these cancer cells were no longer correctly trimmed enzymatically -- in this case by the enzyme ERAAP.

By contrast, the epitopes on the cells of the successfully treated tumour did not require processing by ERAAP and were therefore also not dependent on stimulation by interferon gamma.

According to Textor, epitopes that do not need processing by the enzyme ERAAP are therefore, likely to be a better choice for immunotherapy.

The findings were published in the Journal of Experimental Medicine.