What You Need to Know About Checkpoint Inhibitors

Overview

Checkpoint inhibitors are a type of immunotherapy, a treatment that helps the body's immune system fight cancer. They work by releasing the "brakes" on immune cells, allowing an immune attack against cancer cells. These ground-breaking drugs have produced remarkable responses and led to lasting remissions for many patients with advanced cancers.

Mechanism of Action

Our immune system is equipped with checkpoints—proteins on immune cells that regulate the immune response to prevent autoimmune reactions. However, some cancer cells can exploit these checkpoints to evade detection and attack from the immune system.

Checkpoint inhibitors target and block specific checkpoint proteins on immune cells called T cells or on cancer cells, which prevent the immune system from attacking them. Notable checkpoint proteins targeted by these drugs include:

• PD-1: Programmed death-1 (PD-1) is a protein on the surface of T cells. It interacts with the PD-L1 protein on cancer cells to suppress the immune response. Blocking this interaction allows the immune system to recognize and attack cancer cells.
• CTLA-4: Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is another protein on T cells responsible for inhibiting their activation. Blocking this protein can enhance the immune system's ability to detect and eliminate cancer cells.

Indications and Usage

Checkpoint inhibitors have been approved for treatment across a wide range of cancers, including:

• Non-small cell lung cancer (NSCLC)
• Melanoma
• Bladder cancer
• Head and neck cancer
• Hodgkin lymphoma
• Renal cell carcinoma (kidney cancer)
• Microsatellite instability-high (MSI-H) cancer

It is crucial to note that not every patient is eligible for checkpoint inhibitor therapy, and eligibility depends on factors such as cancer type, stage, prior treatments, and overall health.

Side Effects

While checkpoint inhibitors can be highly effective, they may provoke a range of side effects, predominantly related to an overactive immune system. Some common side effects include:

• Fatigue
• Rash
• Diarrhea
• Nausea
• Decreased appetite

More severe side effects, such as pneumonitis (lung inflammation) or colitis (intestinal inflammation), can be severe—but are relatively rare. It is essential that any new or worsening symptoms are reported to the healthcare team, as early intervention can help reduce complications.

Future Research

Checkpoint inhibitors have revolutionized cancer therapy; however, they are only effective in a subset of patients. Future research aims to enhance their efficacy and identify biomarkers to predict treatment response better. Additionally, there is growing interest in combining checkpoint inhibitors with other treatments, such as targeted therapy, chemotherapy, or radiation, to boost outcomes.