Knowing the effectiveness of immunotherapies is the ultimate goal of a new study on the role of the PDL1 protein against cancer. Immunotherapy aims to enhance the antitumor activity of the immune system to eliminate the disease or slow its progression.
Scientists at the Navarrabiomed Biomedical Research Center have recently released the results of a key study to predict the effectiveness of immunotherapies. The research has been published in the journal Cell Reports.
David Escors, researcher responsible for the Immunomodulation Group of Navarrabiomed, said that there are many tumors resistant to immunotherapy due to mutations in different metabolic pathways of cancer cells. One of such cases is mutation in the interferon signaling pathway.
Interferon is a molecule produced by the lymphocytes of the immune system or can be injected directly into the patient. Its main function is to eliminate the tumor cell by activating a signaling cascade inside it. This mechanism was not known in depth; however, it was observed that patients with mutations in this pathway were resistant to immunotherapy.
In this sense, the group has discovered that the expression of the PDL1 protein in cancer cells has a direct relationship with this resistance, because it creates a barrier that acts as a direct line of defense of the cancer against the treatment, inhibiting the interferon pathway and preventing its antitumor effect.
New line of research
Maria Gato, first author of the article, emphasized the relevance of the findings. “We have discovered which functional domains of the PDL1 protein are necessary to exert its function of protecting the tumor from the interferon treatment. We have also been able to characterize the metabolic pathway through which the antitumor activity that relates them is developed and which are the mutations involved in the functionality of said protein.”
The group started a new line of research with the objective of offering the maximum possible information to the oncologists. In addition, they believe it will help to identify those mutations in PDL1 that predict the therapeutic efficacy in each particular patient against a possible treatment with immunotherapy.