Researchers from the Centre of Biomedical Research Navarrabiomed have recently published the results from a study key in predicting the efficacy of immunotherapies. This study has been published in Cell Reports.
The goal of immunotherapy is potentiating the anti-tumor activities of the human immune system to eliminate cancer cells or stall cancer progression. Drs David Escors and Grazyna Kochan, the supervisors of the study point out that many tumors acquire resistances to therapies through accumulating mutations in particular metabolic pathways. This is the case of acquisition of deleterious mutations in the interferon signal transduction pathway.
Interferons are molecules produced by lymphocytes, or in some cases injected into patients, which kill cancer cells by activating a signal transduction pathway in tumor cells. This mechanism of action is not well understood yet, but it is known that patients exhibiting tumors with inactivating mutations in this pathway were refractory to immunotherapy.
More specifically, the immunomodulation group has discovered that PDL1 expression in cancer cells directly correlates with resistance, because it creates a “force field” that shields cancer cells from interferons, preventing their anti-tumor effects.
Novel research theme
María Gato, PhD student and first author of the paper, highlights the relevance of the study. “Our results will open new avenues for research in immunotherapy, because now we know the functional domains of PDL1 which are required for its anti-interferon activities. Moreover, we have characterized the signal transduction pathway used by PDL1 to interfere with interferons, and which mutations are linked to the activities of PDL1”, remarks the young scientist.
This study has opened up a new research theme that will provide invaluable information to oncologists in their clinical practice. The researchers believe that this research subject will identify mutations in PDL1 with prognostic value for specific patients undergoing immunotherapy.
This study was carried out from 2016 to 2017 with collaborations with the Oncology Department of Complejo Hospitalario de Navarra (CHN), with researchers from the Centro de Investigación Médica Aplicada (CIMA) and the group of cancer signaling from Navarrabiomed. In addition, researchers from the University of Manchester and Free University of Brussels also took part in the study.
This study was carried out as the result of scientific research from Instituto de Investigación Sanitaria de Navarra (IdiSNA), to which the research group and Navarrabiomed belong.
Cell Reports cover Volume 20, Issue 8
The cover image has been made by illustrator Elisa Reta Zubiri, Communication and Design Unit from Navarrabiomed. The cover is a collage, inspired by Jules Verne's From the Earth to the Moon, depicting the main conclusion of the paper by Gato-Cañas et al. The planet represents a cancer cell shielded by a barrier (atmosphere) made of PDL1 molecules. This barrier protects the cell from the incoming “interferon” rockets.