Immunity and cancer : new breakthroughs through epigenetics


Each year, more than 1.6 million new cases of breast cancer are diagnosed. Breast cancer is a very heterogeneous disease, with many known subtypes, so it's actually a combination of several diseases. In recent years, specific therapies adapted to these different subtypes are proposed and greatly improve the effectiveness of patient care. Nevertheless, some subtypes remain difficult to treat and it is more important than ever to deepen our understanding of the molecular mechanisms of these cancers. In this context, epigenetics, a discipline that studies the regulatory mechanisms of our genes independently of any mutation in DNA, has opened new avenues for research.

Researchers from the Laboratory of Epigenetics of Cancer (Faculty of Medicine, U-CRC, Free University of Brussels), led by Prof. François Fuks, in collaboration with the team of the Laboratory of Tumor Biology and Development, led by the Pr. Agnès Noël (GIGA Cancer, University of Liège) were interested in the regulation of breast cancer. Their study also involved teams from the Bordet Institute (Drs Willard-Gallo and Sotiriou as well as IBMM, ULB (Prof. Van Lint).

The goal of the study ? Characterize TET enzymes, responsible for a chemical modification of DNA, hydroxymethylation. These important enzymes intervene in the regulation of genes; they were already known for their key role in many cancers, including breast cancers.

Importantly, the new study unveils a mode of regulation of TET enzymes: in the presence of certain immune cells in the tumor, cancer cells lose these enzymes following an immune response. This dialogue between the immune system and the cancer cells is particularly marked in a distinctive subtype, "basal-like" cancers that remain poorly treated today and constitute a major challenge in breast oncology. The loss of TET enzymes affects the survival prognosis of patients and highlights the influence of the immune system on cancer cells. Moreover, this discovery has been extended to more than a dozen additional cancers, such as cancers of the ovaries, lungs, thyroid, or even melanoma.

These works, financed by an inter-university project of Télévie, as well as by the FNRS and Wallonia, have thus brought to light a new aspect of the regulation of cancers by immune cells. The presence of immune cells in cancers strongly conditions the response of patients to various treatments, including new immunotherapies. Deciphering the molecular mechanisms involved in the dialogue between the immune system and the tumor could therefore lead to improved patient management. The study is published in the journal Science Advances on June 20, 2018.

Prof. Agnès Noël, Directrice du GIGA Cancer, Laboratoire de biologie des tumeurs et du développement

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