Noble prize 2018 Physiology and Medicine

Mortality rates for cancer have increased worldwide increasing the burden on the shoulders of oncologists and clinical scientists to make a significant breakthrough. James Allison and Tasuku Honjo have created a history in discoveries in the field of the inherent ability of the human immune system to fight cancer cells.
The body's immune cells and their functions can be modified such that it helps the body to attack cancer cells more efficiently. These cells can be activated or suppressed as required.
T cells are a type of white blood cells that provide immunity to the body. However, their functions are highly regulated by proteins called immune checkpoints. These proteins may be inhibitory or stimulatory in action. Many scientists including Allison found that CTLA-4, an immune checkpoint protein inhibits the T-cell response.
However, it was Allison who further developed an antibody against CTLA-4. Mice with cancer, when treated with the antibody, had been cured of the disease. Similar results were seen on a study in melanoma patients.
In a different study, Honjo had already discovered another inhibitor protein called PD-1. All cells including cancer cells carry proteins such as antigens on their surface that serve as identification markers. Antigen-presenting cells (APCs) process antigens from the cancer cells and present them on their surface.
When a T-cell encounters an antigen presenting cell (APC), its receptor binds to the antigen. This initiates the activation of T-cell.
However, a molecule called PD-1 present on the surface of T-cells when bound to another protein on the APC acts as a brake and prevents the T-cell from functioning adequately.
This inhibition can be prevented by a therapeutic antibody that blocks PD-1 action and facilitates the function of T-cells.
In Allison’s study, it was discovered that T cells also have an accelerator. CTLA-4 is a protein that has a similar effect to PD1. It inhibits the function of T-cells in turn affecting the activity of the accelerator.
Introducing a therapeutic antibody that blocks CTLA-4 action stops the brake and boosts the immune response by allowing the accelerator to function.
Initial studies showed better results in case of PD-1 therapy, but newer studies show that a combination therapy that targets both proteins can be more effective.
These pioneering studies have set a landmark in the discoveries of anticancer drugs saving the lives of millions.