Scientists at A*STAR's Singapore Immunology Network (SIgN) have discovered a new class of lipids in the leukemia cells that are detected by a unique group of immune cells. By recognising the lipids, the immune cells stimulate an immune response to destroy the leukemia cells and suppress their growth. The newly identified mode of cancer cell recognition by the immune system opens up new possibilities for leukemia immunotherapy.
leukemia is characterized by the accumulation of cancer cells originating from blood cells, in the blood or bone marrow. Current treatments for leukemia largely involve chemotherapy to eradicate all cancer cells, followed by stem cell transplants to restore healthy blood cells in the patients.
In a recent study reported in the Journal of Experimental Medicine (JEM) online, the team co-led by Dr Lucia Mori and Prof Gennaro De Libero identified a new class of lipids, methyl-lysophosphatidic acids (mLPA), which accumulate in leukemia cells. Following which, the team identified a specific group of immune cells, described as mLPA-specific T-cells that are capable of recognising the mLPA in the leukemia cells. The detection triggers an immune response that activates the T cells to kill the leukemia cells and limits cancer progression. The efficacy of the T cells in killing leukemia cells was also demonstrated in a mouse model of human leukemia.
Thus far, only proteins in cancer cells have been known to activate T cells. This study is a pioneer in its discovery of mLPA, and the specific T cells which can identify lipids expressed by cancer cells. Unlike proteins, lipids in cancer cells do not differ between individuals, indicating that the recognition of mLPA by mLPA-specific T-cells happens in all leukemia patients. This new mode of cancer cell recognition suggests that the T-cells can potentially be harnessed for a leukemia immunotherapy that is effective in all patients.
"The identification of mLPA and its role in activating specific T cells is novel. This knowledge not only sheds light on future leukemia studies, but also complements ongoing leukemia immunotherapy studies focusing on proteins in cancer cells," said Dr Lucia Mori, Principal Investigator at SIgN. "Current treatments run the risk of failure due to re-growth of residual leukemia cells that survive after stem cell transplants. T-cell immunotherapy may serve as a complementary treatment for more effective and safer therapeutic approach towards leukemia."
Professor Laurent Renia, Acting Executive Director of SIgN, said, "At SIgN, we study how the human immune system protects us naturally from infections. We engage in promising disease-specific research projects that ultimately pave the way for the development of treatments and drugs which can better combat these diseases. A pertinent example will be this study; this mode of immune recognition of leukemia cells is an insightful discovery that will create new opportunities for immunotherapy to improve the lives of leukemia patients."
The above story is based on materials provided by A*Star Agency for Science, Technology and Research. Note: Materials may be edited for content and length.
- M. Lepore, C. de Lalla, S. R. Gundimeda, H. Gsellinger, M. Consonni, C. Garavaglia, S. Sansano, F. Piccolo, A. Scelfo, D. Haussinger, D. Montagna, F. Locatelli, C. Bonini, A. Bondanza, A. Forcina, Z. Li, G. Ni, F. Ciceri, P. Jeno, C. Xia, L. Mori, P. Dellabona, G. Casorati, G. De Libero. A novel self-lipid antigen targets human T cells against CD1c leukemias. Journal of Experimental Medicine, 2014; DOI: 10.1084/jem.20140410
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