Lipids lure T-Cells to lynch leukemia

T cells (yellow) recognize and attack leukemia cells (green). (Illustration: University of Basel, Artem Kalinichenko)

Current therapies to treat Leukemia, a group of cancers that affects blood cells, involve chemotherapy to eradicate tumors, followed by bone-marrow stem cell transplants to help the patient regenerate healthy blood cells. But it’s not always effective. In some acute cases, leukemia cells survive this treatment and start to re-grow. New research published in the Journal of Experimental Medicine by scientists at the University of Basel has come up with a new way to detect and eradicate leukemia cells before a second outbreak of the disease.

In the body, T lymphocytes, or T cells are the sentinels that destroy infected and tumor cells. Some tumor cells produce large amounts of protein antigens that T cells can recognize. These tumor-specific protein antigens, also called tumor-associated antigens (TAA) can activate and stimulate specific T cells, which in turn kill leukemia cells. But, it’s not quite as simple to target tumors by these protein TAA because variant leukemia cells can both reduce their numbers as well as change their structure to such a degree that T-cells fail to recognize them.

Dr. Gennaro De Libero, along with Dr. Marco Lepore and a 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 recognizing leukemia cells, by drawing attention to lipid molecules that can act as stand-ins for the protein TAA.

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

“We have discovered a unique class of lipid molecules able to stimulate the T-cells of the immune system that kill leukaemia cells,” said coauthor Dr. Lucia Mori at the Department of Biomedicine at Basel. “It was a so far unknown lipid molecule.”

Large amounts of the new lipid, methyl-lysophosphatidic acid (mLPA), were discovered to present in several forms of human leukemias. “So far, only proteins present in cancer cells were known to activate T cells. Our study is the first discovering T cells, which target lipids expressed by cancer cells,” said Mori.

The mLPA lipid is unique and useful in that, unlike protein TAA, its structure does not change in variant leukemias and that it remains abundant in leukemia cells. The researchers are now investigating whether mLPA can be used to target leukemia cells in addition to protein TAA.

The multiple strategies adopted by the immune system to fight cancer are quite surprising, said Mori. The newly identified mode of cancer cell recognition by immune cells opens up new possibilities for novel non-invasive leukemia immunotherapy, she said. This type of immunotherapy may be extremely beneficial in preventing relapses of the disease after chemotherapy and bone marrow transplantation.

In 2010, globally, approximately 2,81,500 people died of leukemia. It is the most common kind of cancer to affect children.

The researchers’ next step is to “empower T cells of leukemia patients, in particular children, with the genes that allow them to recognize lipid molecules and kill cancer cells,” said Mori.

This piece originally appeared in Popular Science India. Reprinted with permission. Chhavi Sachdev reserves the right to be identified as its author.

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