T cells use a novel mechanism to fight leukaemia.

They may recognise unique lipids produced by cancer cells and kill tumour cells expressing these lipid molecules.

A study conducted by researchers at the University of Basel shows that a tumour-associated lipid stimulates specific T cells, which efficiently kill leukaemia cells both in vitro and in animal models.

The results have been published in the Journal of Experimental Medicine.

Leukemias are cancer diseases affecting blood cells.

Acute leukaemias prevent development of normal blood cells and thereby are severe life-threatening diseases.

Current therapy for acute leukaemias is based on chemotherapy that eradicates tumour cells followed by bone-marrow stem cell transplantation that reconstitutes the patient with healthy blood cells.

In some cases, leukaemia cells survive this treatment and start to re-grow.

A major aim of many studies is finding novel and efficient ways to detect and eradicate leukaemia cells before a second outbreak of the disease.

More punch against tumour cells

T lymphocytes are major contributors to fight against leukaemias.

T cells may recognise and become activated by tumour-specific protein antigens in some instances produced in large amounts only by tumour cells.

These protein antigens are also called tumour-associated antigens (TAA) and stimulate specific T cells, which in turn kill leukaemia cells.

However, protein TAA accumulation can be drastically reduced by variant leukaemia cells and some TAA may change their structure, thus preventing recognition by T cells and facilitating tumour immune evasion.

Prof. Gennaro De Libero and his team from the Department of Biomedicine at the University of Basel has identified a new approach that might help to make the immune system more efficient in recognising leukaemia cells.

His research team is studying T cells that specifically recognise lipid antigens for several years.

Together with colleagues in Italy, China and Singapore, the Swiss team has identified a new lipid that accumulates in leukaemia cells and that stimulates specific T cell responses.

The new lipid methyl-lysophosphatidic acid (mLPA) is very abundant in several forms of human leukaemias and is the first example of a lipid TAA.

Therapeutic implications in human leukaemia

The published study also shows that it is possible to isolate human T cells that specifically recognise and kill mLPA-expressing leukaemia cells in in vitro tests.

When these T cells were transplanted into mice, they also displayed great in vivo therapeutic efficacy against leukaemia cells.

An important feature of mLPA is that differently from protein TAA, it does not change its structure, and remains abundant in leukaemia cells.

The Swiss team is now investigating whether mLPA can be used to target leukaemia cells in addition to protein TAA.

This type of immunotherapy may be extremely beneficial in preventing relapses of the disease after chemotherapy and bone marrow transplantation, opening new avenues to novel non-invasive cancer immunotherapies.

Source: Basel University