Immune Checkpoint Blockade, or ICB therapy, has become the gold standard for treating lung cancer because of its frequently successful results.

High levels of the PD-L1 protein have served as the main indicator of a favourable response to treatment up until now.

Yet, despite having naturally high amounts of this protein, many lung cancer tumours do not react to ICB treatment; in contrast, tumours with low levels of the same protein do.

Patients may live longer and healthier lives if it is known in advance which patients will react strongly. This could also save valuable time. The ICB treatments inhibit the action of PD-L1 and its partner PD1, to increase the action of the immune system against the tumour cells.

These two proteins are part of a natural system to avoid autoimmunity, with PD-L1 being typically present in the membrane of the cells (including cancer cells) and, through the interaction with its partner PD-1, present in immune cells, prevent an overaction of the immune system that can be detrimental for the organism.

In the context of a tumour, this results in the immune system not killing cancer cells, hence why the ICB treatment attempts to block this contact.

On the other hand, tumours are found with low levels of PD-L1. Without this immune-limiting trick, how are they avoiding a strong immune attack? In a recent publication in the scientific journal Cell Reports Medicine, the team led by Dr. Sanchez-Cespedes reports that many of the tumours with low PD-L1 have developed genetic strategies that avoid the action of the gamma interferon against the tumour cells.

The gamma interferon is a powerful stimulator of the immune response secreted by immune cells and, avoiding its action, the tumour cells cannot be killed by the immune system.

One of these genetic strategies found in tumour cells is the activation of the oncogene MYC, which leads to a cascade of events that prevent the action of the gamma interferon inside the cell.

Experimental results show that this could be a strong and reliable predictor of response to ICB in cancer patients, as tumours with MYC genetic activation are associated with a poorer prognosis after treatment with ICBs.