Lung cancer: molecular advances

New discoveries in the treatment of lung cancer: the role of the Bcl-xL protein in the aging of neutrophils, the white blood cells that contribute to tumor development.

Neutrophils are white blood cells essential to our defense against bacterial infection. These cells patrol the body for 1 or 2 days, then die and are replaced by new neutrophils. In many cancers, their presence in large quantities in the blood or in the tumor is often associated with a poor prognosis, suggesting that these cells play a role in tumor development.

Researchers - including a team from Biopark Charleroi - have studied these neutrophils in the most deadly cancer in both men and women, lung cancer. Using sophisticated mouse models, these research groups, including Etienne Meylan’s (Lung Cancer & Immuno-Oncology laboratory, Institut Bordet, Faculty of Medicine and Laboratoire d’Immunobiologie, Faculty of Science), have recently observed that neutrophils entering the tumor may have a longer lifespan than other neutrophils, and that this longevity confers functions that favor disease progression.

In their study published in the journal EMBO Molecular Medicine, Etienne Meylan and his laboratory have demonstrated the molecular mechanisms that enable neutrophils to survive long in the tumor. They revealed that a protein called Bcl-xL was essential for the aging of tumor-associated neutrophils. Anita Bodac, PhD student and first author of this study, enthuses: "By discovering a large quantity of Bcl-xL in neutrophils localized inside tumors, in our models as well as in patients, we wanted to block this protein in order to prevent their aging".

This idea paid off: by specifically targeting this protein with a pharmacological approach, the researchers were able to reduce neutrophil aging without disturbing the normal neutrophils that are essential to our anti-bacterial defense. In the tumor, the researchers observed that the treatment caused old neutrophils to be replaced by young ones. "We think this is an important observation, because the young neutrophils certainly include cells with anti-tumor capabilities," continues Anita. This treatment alone reduced tumour growth in mouse models of lung adenocarcinoma. These results therefore suggest that it is possible to target a subgroup of pro-tumor neutrophils while preserving other neutrophils. Prof. Meylan concludes: "In the era of immunotherapy, many new treatments are aimed at activating or reactivating T lymphocytes to destroy cancer. Other immune cells, such as neutrophils, will certainly be considered in the future to obtain better responses to existing therapies.