What are immune checkpoint inhibitors?

In a healthy body, "cytotoxic or killer T cells" are the main immune cells which actively kill infected cells or cancerous cells.  Once killer T cells eliminate infected cells, they need to be turned off to prevent overactivated T cells from killing healthy cells.  The immune checkpoint proteins turn off the activity of T cells by engaging with the surface proteins of killer T cells.   

Unfortunately, some of the cancer cells co-opt this regulatory system by producing a lot of these immune checkpoint proteins to inhibit the function of T cells, so that they can evade the immune system. 

Immunotherapy drug called Immune checkpoint inhibitors block the engagement of immune checkpoint proteins of cancer cells with killer T cells.  Programmed death- ligand 1 (PD-L1) and CD80/86 are immune checkpoint proteins that cancer cells frequently produce in high numbers. Pembrolizumab, nivolumab, durvalumab and atezolizumab block the engagement of PD-L1 in tumor cells and PD-1 in killer T cells, and thus free those cells to do their job, which is killing cancerous cells.  Ipilimumab blocks the engagement of CD80/86 in cancer cells and cytotoxic T-lymphocyte-associated protein (CTLA)-4 on the surface of killer T cells. 

In the phase 3, KEYNOTE-024 clinical trial, 31.9% of the metastatic non-small cell lung cancer patients treated with pembrolizumab are still alive after 5 years of the initial diagnosis.  Before the approval of pembrolizumab, the fiver year survival rate for the patients with metastatic non-small cell lung cancer was just 5%.   Immune checkpoint inhibitors have been truly ground-breaking therapies for the patients with many different types of cancer.  However, the recent results with pembrolizumab and nivolumab for the glioblastoma patients have been disappointing.  

Although they have less side effects than chemotherapy, immune-related adverse effects such as pneumonitis, hepatitis, pancreatitis or myocarditis can occur.