The team led by Dr. Manel Esteller discovers an important advance to treat lung cancer

A team led by Manel Esteller has discovered an epigenetic signature that allows predicting the response in lung cancer to therapy with the anti-PD-1 antibody, the most frequently used immunotherapy in oncology. The advance, which has just been published in the journal The Lancet Respiratory Medicine, the most prestigious publication in the area of biology and lung diseases, is part of a clinical trial funded by Obra Social "la Caixa" and started two years ago, in which 100 patients are participating.

These results will be key to the application of the most appropriate therapy for each patient with the aim of prolonging and improving their quality of life and reducing the impact of treatment toxicity.

Immunotherapy is revolutionizing cancer treatment. Our immune system is responsible, in addition to fighting microorganisms responsible for infections, for eliminating harmful cells such as those transformed into tumors. But when cancer appears, this means that its cells have learned to hide from our immune system, which does not recognize them and therefore does not destroy them.

Current immunotherapy manages to remove that disguise from the cancerous cell, and then our defense cells, such as T and B lymphocytes, can act against it. However, there are various types of tumors against which immunotherapy is ineffective. Even within immunosensitive ones, such as lung, melanoma, and kidney cancer, only 30-40% respond effectively long-term to it. Therefore, it is important to know in advance whether a tumor will be sensitive or not to immunotherapy, also considering that these are expensive drugs and not without side effects.

The conclusions of the work, which is focusing on colon and lung tumors due to their high incidence, and on pancreatic and brain tumors due to their high mortality, delve into a promising path for the future treatment of cancer. "Epigenetic signals, such as DNA methylation, act as electrical switches that turn thousands of our genes on or off. Therefore, we believe that they should also participate in the programs that the tumor cell uses to escape the control of the immune system," explains Dr. Manel Esteller.

Specifically, and in relation to the research published in The Lancet Respiratory Medicine, the researcher points out that "studying hundreds of lung tumors, we realized that those that presented a specific epigenetic footprint, which we have called EPIMMUNE, responded very well to chemotherapy compared to those that lacked it. This EPIMMUNE signature is found in a third of lung cancers and presents an enrichment in T and B lymphocytes, while patients who do not respond to therapy present a "cold" tumor microenvironment with immunity-inhibiting cells."

"Now we want to extend this type of epigenetic studies to other tumor types and to other immunotherapies, such as using anti-PD-L1 or anti-CTLA4 antibodies," explains Esteller.

The researcher also wanted to highlight that "the advance is the result of the sum of efforts of basic, applied, and clinical researchers, as well as the combination of public investment and foundations such as the "la Caixa" Social Work, without which this work would not have been possible."

Cancer is the leading cause of mortality in the West, along with cardiovascular diseases. Every year, eight million people die from cancer worldwide, 100,000 in Spain, and about 17,000 in Catalonia. It is a condition caused by genetic alterations, but also by epigenetic alterations. Hereditary cancers represent only 10% of the total, while the other 90% are sporadic tumors. It is known that lung, throat, and mouth cancers are mainly due to tobacco, but the cause of other tumors, such as breast cancer, is unknown. What is clear is that the epigenetic contribution is very important in the formation of sporadic tumors.