Gaining ground in the battle against lung cancer
More than one million people worldwide die each year from lung cancer. Oncologists are turning to immunotherapy as a new treatment option. This uses the body’s own immune system and stimulates immune reactions which decelerate or even halt the growth of cancer cells. Scientists at Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) have now succeeded in proving that a certain protein in the cell nucleus regulates the immune response and makes a significant contribution to the fight against lung carcinoma. The findings were published in the specialist journal Cancer Research.
The team of scientists led by Prof. Dr. Susetta Finotto, head of the Department of Molecular Pneumology at Universitätsklinikum Erlangen, had already proven that lung tumours are capable of reprogramming the immune response using a special protein. This leads to the cells responsible for the immune reaction being switched off, and tumour cells avoid being targeted by the immune system.
Now, the researchers have made another exciting discovery. They discovered that the protein NFATc1 has an important role to play in defending against tumours, and were able to link it to lung cancer for the first time.
Within the cell’s nucleus, the transcription factor NFATc1 regulates the manifestation of various genes, which in turn determine the function of the so-called cytotoxic T-cells. ‘NFATc1 encourages the creation of cytotoxic molecules and can therefore induce cell death in tumour cells,’ says the doctoral candidate Lisanne Heim.
The working group observed a progressive decrease in NFATc1 in the lung tumour tissue of non-small cell lung carcinoma in patients at an advanced stage of the disease. The results indicate that NFATc1 is significant for the functional regeneration of T-cells, which are hindered during the development of the tumour.
During the study, Lisanne Heim followed the advice of Prof. Dr. Susetta Finotto and also investigated the so-called checkpoint inhibitors, which are used in cancer immunotherapy. Instead of tackling cancer cells directly, the molecules attack at important places in the immune system, boosting the body’s own immune mechanisms. Lisanne Heim investigated the signal pathways of anti-PD1 antibodies in connection with NFATc1. ‘There is a higher proportion of NFATc1 in T-cells when anti-PD1 antibodies are used, which leads to a more pronounced anti-tumour immune response,’ explains the young researcher. The researchers demonstrated that conditionally inactivating NFATc1 in T-cells led to increased lung tumour growth. ‘We were able to show that this is associated with impaired T-cell activation and function.’
The current research findings make a contribution to our understanding of the mechanisms behind how anti-PD1 antibodies work, enabling more successful immunotherapy approaches aimed at fighting the spread of lung cancer to be used in a clinical setting.
Prof. Dr. Susetta Finotto
Phone: +49 9131 8535883
Lisanne Heim, Juliane Friedrich, Marina Engelhardt, Denis Iulian Trufa, Carol-Immanuel Geppert, Ralf Joachim Rieker, Horia Sirbu, Susetta Finotto: NFATc1 Promotes Antitumoral Effector Functions and Memory CD8+ T-cell Differentiation during Non-Small Cell Lung Cancer Development. doi: 10.1158/0008-5472.CAN-17-3297