Researchers discover a new epigenetic signature which predicts the response to immunotherapy in lung cancer


An article published in the journal The Lancet Respiratory Medicine, led by Professor Manel Esteller, ICREA researcher and Director of the Cancer Epigenetics and Biology Program (PEBC) in the Bellvitge Biomedical Research Institute (IDIBELL), shows a pattern of epigenetic alterations in lung cancer that can predict whether the tumor will respond to the therapy with anti-PD-1 antibodies, the most common immunotherapy in oncology.

“Sometimes, tumor cells manage to hide so that our immune system, which is usually efficient, does not recognize them and therefore it does not destroy them. The current immunotherapy can remove this “disguise” from the cancer cells so that our defence cells, such as T and B lymphocytes act against them”, says Esteller. However, there are different types of tumors to which immunotherapy is not efficient. Even with immunosensitive ones, such as lung or kidney cancer, or melanoma, about a 30-40 % respond efficiently on the long run. “Therefore, it is important to know in advance whether a tumor will be responsive to the immunotherapy, bearing in mind, in addition, that these drugs are expensive and can have adverse effects”, adds the researcher.

“Epigenetic signals, such as DNA methylation, act as a switch turning our genes on and off. Therefore we think these should take part in the program the tumor cell uses to escape the immune system control”, says Esteller. Through the study of hundreds of lung cancers, IDIBELL-UB researchers saw those showing a specific epigenetic signal, named EPIMMUNE, responded well to immunotherapy compared to those that didn’t have it. EPIMMUNE is found in a third part of lung cancers and is related to T and B lymphocyte increase.

With these results, the team wants to continue studying this research line. “We want to spread this kind of study to other types of tumor cancers and other immunotherapies, using anti-PD-L1 or anti-CTCLA4 antibodies, for instance. Also, this study is an example of the combined efforts of basic, applied and clinical researchers and the combination of public funding and financial support from “la Caixa” foundation, without which this research study would not have been possible”, Esteller highlights.


Article Reference:

Duruisseaux, M.; Martínez-Cardús, A.; Calleja-Cervantes, M. E.; Morán, S.; Castro de Moura, M.; Dávalos, V.; Piñeyro, D.; Sánchez-Céspedes, M.; Girard, N.; Breve, M.; Giroux-Leprieur, E.; Dumenil, C.; Pradotto, M.; Bironzo, P.; Capelleto, E.; Novello, S.; Cortot, A.; Copin, M. C.; Karachaliou, N.; González-Cao, M.; Peralta, S.; Montuenga, L. M.; Gil-Bazo, I.; Baraibar, I.; Lozano, M. D.; Varela, M.; Ruffinelli, J. C.; Palmero, R.; Nadal, E.; Morán, T.; Pérez, L.; Ramos, I.; Xiao, Q.; Fernández, A. F.; Fraga, M. F.; Gut, M.; Gut, I.; Teixidó, C.; Vilariño, N.; Prat, A.; Reguart, N.; Benito, A.; Garrido, P.; Barragan, I.; Emile, J. F.; Rosell, R.; Brambilla, E.; Esteller, M. «Epigenetic prediction of response to anti-PD-1 treatment in non-small-cell lung cancer: a multicenter, retrospective analysis»The Lancet Respiratory Medicine, 2018. Doi: 10.1016/S2213-2600(18)30284-4


Universitat de Barcelona