Patients with advanced or difficult-to-treat cancers now have hope thanks to immune checkpoint inhibitors, a breakthrough in cancer treatment. Unlike traditional therapies, these drugs enable your immune system to identify and eliminate cancer cells that target them directly. Checkpoint inhibitors “release the brakes” on immune cells, enabling them to more effectively fight cancer by blocking particular proteins (such as PD-1, PD-L1, and CTLA-4) that typically limit immune responses.
What are checkpoint inhibitors?
These are the types of drugs that block checkpoint proteins affecting the immune system and help immune cells to better fight cancerous cells. These help target many cancers, like melanoma and skin cancer. Beyond these cancers, some of the other cancers they can also target.
What are the different cancers treated by Immune checkpoint inhibitors?
- Lung cancer(non-small cell and small cell)
- Breast cancer (specifically, triple-negative breast cancer)
- Kidney cancer
- Head and neck cancers
- Bladder cancer
- Hodgkin lymphoma
- Colorectal cancer
- Liver cancer
- Stomach and esophageal cancers
- Cervical cancer
- Endometrial cancer
Note: Any solid tumor that is not able to repair DNA damage can be treated.
What key checkpoint proteins are targeted?
Medicines, also known as Monoclonal antibodies, can be designed to target these checkpoint inhibitors; these drugs do not act directly but helps the immune system to fight off the cancerous cells effectively.
The type of checkpoint inhibitor includes:
- PD-1 (programmed cell death protein 1)
- PD-L1 (programmed cell death ligand 1)
- CTLA-4 (cytotoxic T lymphocyte-associated protein 4)
- LAG-3 (lymphocyte activation gene 3)
PD-1/PD-L1 inhibitors: PD-1 is a checkpoint protein found on T cells,. It usually acts as a kind of “switch-off button” to prevent T cells from attacking other cells in the body. This occurs when it binds to PD-L1, a protein found on certain healthy (and cancerous) cells. The T cell is essentially directed to leave the other cell alone when PD-1 binds to PD-L1. High levels of PD-L1 help some cancer cells escape an immune attack.
PD-1 Inhibitor drugs
- Nivolumab
- Pembrolizumab (Keytruda)
- Cemiplimab (for advanced skin cancer, like squamous cell carcinoma)
PD-L1 Inhibitor drugs
- Atezolizumab
- Avelumab
- Durvalumab (Imfinzi)
CTLA-4 Inhibitors: These drugs also act on T cells by blocking the CTLA-4 protein to enhance immune response and can be used along with PD-1/PD-L1 to keep a check on the immune system. CTLA-4 inhibitors are
- Ipilimumab (used to treat advanced melanoma and renal cancer)
- tremelimumab
Ipilimumab, along with PD-1, can be used to treat
- Melanoma
- Mesothelioma
- Bowel cancer
- Lung cancer (non-small cell)
LAG-3: Relatlimab is the inhibitor drug that blocks the LAG-3 protein present on some of the immune cells and can be given along with nivolumab (PD-1 inhibitor drug), in a combination called Opdualag that can be used to treat advanced melanoma.
What are the common side effects of checkpoint inhibitor drugs?
Side effects depend upon your cancer type, stage, overall health, and the type of checkpoint Inhibitor drug used or during the cancer treatment, when these drugs are administered.
Some of the general side effects are:
- Allergic reactions such as Skin rash, difficulty breathing, swelling, and redness
- Diarrhoea
- Fatigue.
- Loss of appetite
- Cough
Some rare side effects can cause severe health conditions due to widespread inflammation; depending on the body parts, these include:
- Dry and itchy skin
- Chest pain (due to lung inflammation)
- Belly pain (due to the colon inflammation)
- Diabetes (Inflammation in the pancreas)
- Hepatitis (inflammation of the liver)
- Myocarditis (inflammation in cardiac muscle)
- Nephritis (inflammation in the kidneys)
- Hypophysitis (Inflammation of the pituitary gland)
- Thyroid disease
How Do Immune Checkpoint Inhibitors Help Fight Cancer?
- Activate the Immune System: Your immune system activates, and T cells are deployed to recognize and kill abnormal cells, including cancer.
- Regulate T Cell Activity with Checkpoints: T cells use checkpoint proteins (like PD-1 and CTLA-4) that act as brakes to prevent attacking healthy cells.
- Cancer Hijacks the System: Tumour cells produce large amounts of PD-L1. Binding of PD-L1 to PD-1 on T cells leads to an “OFF” signal, deactivating the T cells.
- T Cells Stop Fighting: The immune system fails to recognise the cancer, and the tumour grows unchecked.
- Introduce Checkpoint Inhibitor Therapy: Administer drugs that block PD-1, PD-L1, or CTLA-4 to prevent checkpoint binding.
- Block the “OFF” Signal: The stop signal is interrupted, and T cells stay active and aggressive.
- T Cells Attack the Tumour: T cells recognise cancer cells and target and destroy them.
- Achieve Tumour Control: The tumour shrinks, stabilises, or goes into remission, immune system continues monitoring and fighting as needed.
A final thought
Immune checkpoint inhibitors have revolutionised the treatment of cancer by using your body’s immune system instead of attacking the tumour directly. For many patients, they provide hope, long-lasting results, and an innovative approach to the battle against cancer, even though they are not appropriate for everyone. Working closely with your medical team and keeping yourself informed can make all the difference.
Moving Forward with Treatment:
- Discuss whether checkpoint inhibitors are appropriate for your cancer type and stage with your oncologist.
- Ask about biomarker testing, such as PD-L1 expression, which can be used to predict how you will react to treatment.
- During treatment, be aware of possible side effects and report any new symptoms right away.
- If standard options aren’t working, look into clinical trials—checkpoint therapies are developing quickly.
FAQs
What are immune checkpoints?
They help control the immune response by turning T cells ON to attack harmful cells and some OFF to prevent damage to healthy tissues.
Do these drugs kill cancer directly?
No. They don’t kill cancer cells directly. Instead, they help your immune system recognise and destroy the cancer.
Are checkpoint inhibitors effective for all cancer types?
Not always. They are most effective in cancers like melanoma, lung, bladder, kidney, and some blood cancers. A test for PD-L1 levels or other biomarkers helps to decide.
Why are checkpoints important for our immune system?
They act like a braking system for the immune system to prevent autoimmunity and slow down the immune attack to restore balance.
What are the side effects I should watch out for?
Watch for side effects such as inflammation in the lungs, liver, intestines, or glands. Always report new symptoms early.
