Immune checkpoint pathway

Many lung cancers coexist with T cells capable of killing the cancer cells. However, the immune system has many normal mechanisms for dampening itself down. The immune system has fail-safe mechanisms that are designed to suppress the immune response at appropriate times in order to minimize damage to healthy tissue. These mechanisms are called immune checkpoint pathways. They are essentially the brakes on the immune system.

In many lung cancer cases, T cells capable of attacking cancer cells are present. However, the immune system has built-in mechanisms to regulate its activity, known as immune checkpoint pathways. These pathways act like brakes, controlling the immune response to prevent excessive damage to healthy tissues.

PD-L1 and PD-1 are types of checkpoint proteins. PD-L1 is found on normal tissue surface and healthy cells, while PD-1 is often found on a type of white blood cells called T-cells, which are responsible for our immune defense. Some cancers disguise themselves by making their own PD-L1. When this happens, it binds to PD-1 on T-cells.

These cells are then not spotted by the checkpoints which means the immune system does not destroy them. Undetected, the cancer cells can continue to grow without being slowed down or stopped.

Immunotherapy treatment with agents inhibitors of PD-1 or PD-L1, reactivates the immune system, helping it to recognize and attack the abnormal cancer cells. Some checkpoint inhibitors work by binding or sticking to the PD-1 on T-cells or PD-L1 on tumor cells.

Immunotherapies stop PD-1 from binding to the PD-L1 on cancer cells. When this happens, the cancer cells can no longer trick the immune system. Another important feature of immunotherapy, is that it creates an immune memory. Therefore, if cancer recurs after initial treatment, our immune system ‘remembers’ and attacks the newly- relapsing cancer cells, thus preventing the cancer to come back. This is how immunotherapy has revolutionized lung cancer treatment: it can achieve a response by reducing or destroying the tumor but most importantly it can maintain that response for a long time, offering significant survival benefits to lung cancer patients.